After 35 days of treatment, the animals were sacrificed and examined for gross tumor formation. A second group of mice underwent screening MRI to detect HCC at older than 6 months of life. Sixteen mice with index lesions (HCC) underwent determination of baseline tumor growth and were randomized to receive daily orogavage of either HPMT vehicle or PD0325901 (20 mg/kg). Serial MRIs were performed biweekly, and the tumor volume was determined. At the time of sacrifice, representative liver sections from different lobes were fixed in 10% formalin, paraffin embedded, and serially cut (5 μm). In vivo proton magnetic

resonance imaging ([1H]-MRI) of the mice with orthotopic tumors were selleckchem performed biweekly using a 9.4-Tesla, 31-cm horizontal bore system (Varian Inc, Palo Alto, CA) equipped with a 12-cm-diameter shielded gradient set capable of up to 38 gauss/cm gradient strength in three directions. The mice were anesthetized with 0.75% isofluorane delivered in medical air at 1 L/minute using a nose mask connected to a gas anesthesia machine (Vetland, Louisville, KY). The animal was positioned inside a 30-mm-diameter and 25-mm-high loop-gap volume coil tuned to 400 MHz. Warm air was blown through the magnet bore to maintain the

animal core body temperature at 35°C selleck chemicals to 37°C, which was monitored with a fiber optic rectal probe (FISO Technologies, Quebec, Canada). Transaxial proton-density weighted images with fat suppression were obtained using a multi-slice spin-echo sequence and the following imaging parameters: field of view, 3 × 3 cm, slice thickness = 1 mm, number of slices = 20, matrix size = 256 × 128, signal averages = 2, repetition time (TR) = 1500 ms, and echo time (TE) = 15 msec. The total image data collection time was approximately 9 minutes. click here Tumor area was calculated by drawing a region of interest on the liver tumor slices using the Varian Browser software.

The area of tumor in each slice was multiplied by the slice thickness plus slice gap to calculate tumor volume per slice. The total tumor volume was obtained by adding the total area of all slices. Immunohistochemistry to detect DNA fragmentation was performed on formalin-fixed, paraffin-embedded liver sections using ApopTag Peroxidase In Situ Apoptosis Detection Kit (Millipore, Billerica, MA). Positively stained cells were counted in four fields (400×) with the highest density of staining per slide and expressed as a percentage relative to the total number of cells. The Fisher’s exact test was used for comparison of two groups with one observed variable. The Student t test was used for comparison of two groups, with P < 0.05 considered significant. The TAMH cell line, derived from TGF-α transgenic mouse hepatocytes, was exposed to PD0325901 (0-100 nM) for 1 or 24 hours. MEK activity reflected by the level of active, phosphorylated ERK (P-ERK) was determined by immunoblot (Fig. 1A).

Therefore, we investigated the patients with repeated overt OGIB in terms of clinical data and medication. Methods: We retrospectively reviewed the clinical records of 81 patients, who referred to our hospital due to overt OGIB between January 2011 and June 2014. Results: Fifteen (18.5%; 11 men, 4 women, mean age 70.2 ± 10.2 years) of 81 patients had repeated overt OGIB. Small intestinal lesions were detected in 11 patients (73.3%) by DBE. Hemostatic therapy was performed in 6 (54.5%) of those patients. However, rebleeding was occurred in five (83.3%) of

six patients with hemostatic therapy. Underlying illness of 15 patients were as follows; 3 cases of heart valve disease (20%), 8 cases of heart disorder (13.3%), 2 cases of abdominal aortic aneurysm (13.3%), 4 cases of chronic http://www.selleckchem.com/products/MLN8237.html renal failure (26.7%), 3 cases of dialysis treatment (20%). Oral medications were as follows: 6 anticoagulant drug (40%), 2 low dose aspirin (13.3%), 1 antiplatelet drug (6.7%). Twelve (80%) patients with repeated overt OGIB received transfusion. The rate of transfusion was significantly higher in patients with repeated overt OGIB when compared with patients with single overt OGIB (p < 0.05). Conclusion: Anticoagulant

JQ1 manufacturer may be the risk for repeated overt OGIB, and the patients with repeated overt OGIB tend to have severe bleeding. Key Word(s): 1. obscure gastrointestinal bleeding; 2. rebleeding Presenting Author: BOON EU ANDREW KWEK Additional Authors: TECK KIANG MALCOLM TAN, TIING LEONG ANG, ENG KIONG TEO, KWONG MING FOCK Corresponding Author: BOON EU ANDREW KWEK Affiliations: Changi General Hospital, Changi General Hospital, Changi General Hospital, Changi General Hospital Objective: Surveillance endoscopy is performed to confirm ulcer healing and absence of cancer in patients with gastric ulcer. Although not routine in patients with simple duodenal ulcers (DU), endoscopy may be repeated in patients with complicated

ulcers to ensure adequate healing prior to commencing anti-thrombotic agents or discontinuing proton pump inhibitor (PPI). We aimed to determine the healing rate of complicated DUs, predictors of delayed healing and the clinical impact of surveillance endoscopy in these patients. Methods: Data selleck inhibitor was collected between March 2010 and January 2013, from consecutive patients admitted for DU bleeding who had endoscopic, angiographic or surgical management. All patients had surveillance endoscopy after 4 or more weeks of PPI therapy. Patient demographics, location and morphology of ulcers, types of intervention and treatment, and co-morbidities were analyzed. The main outcome variables were ulcer healing and clinical predictors of ulcer persistence. Results: 421 patients presented with acute DU bleeding during the study period, of which 77 met study criteria and were analysed; 47 males, 30 females. Mean age was 66.4 years; range 18–88.

Therefore, we investigated the patients with repeated overt OGIB in terms of clinical data and medication. Methods: We retrospectively reviewed the clinical records of 81 patients, who referred to our hospital due to overt OGIB between January 2011 and June 2014. Results: Fifteen (18.5%; 11 men, 4 women, mean age 70.2 ± 10.2 years) of 81 patients had repeated overt OGIB. Small intestinal lesions were detected in 11 patients (73.3%) by DBE. Hemostatic therapy was performed in 6 (54.5%) of those patients. However, rebleeding was occurred in five (83.3%) of

six patients with hemostatic therapy. Underlying illness of 15 patients were as follows; 3 cases of heart valve disease (20%), 8 cases of heart disorder (13.3%), 2 cases of abdominal aortic aneurysm (13.3%), 4 cases of chronic SRT1720 mw renal failure (26.7%), 3 cases of dialysis treatment (20%). Oral medications were as follows: 6 anticoagulant drug (40%), 2 low dose aspirin (13.3%), 1 antiplatelet drug (6.7%). Twelve (80%) patients with repeated overt OGIB received transfusion. The rate of transfusion was significantly higher in patients with repeated overt OGIB when compared with patients with single overt OGIB (p < 0.05). Conclusion: Anticoagulant

selleck compound may be the risk for repeated overt OGIB, and the patients with repeated overt OGIB tend to have severe bleeding. Key Word(s): 1. obscure gastrointestinal bleeding; 2. rebleeding Presenting Author: BOON EU ANDREW KWEK Additional Authors: TECK KIANG MALCOLM TAN, TIING LEONG ANG, ENG KIONG TEO, KWONG MING FOCK Corresponding Author: BOON EU ANDREW KWEK Affiliations: Changi General Hospital, Changi General Hospital, Changi General Hospital, Changi General Hospital Objective: Surveillance endoscopy is performed to confirm ulcer healing and absence of cancer in patients with gastric ulcer. Although not routine in patients with simple duodenal ulcers (DU), endoscopy may be repeated in patients with complicated

ulcers to ensure adequate healing prior to commencing anti-thrombotic agents or discontinuing proton pump inhibitor (PPI). We aimed to determine the healing rate of complicated DUs, predictors of delayed healing and the clinical impact of surveillance endoscopy in these patients. Methods: Data selleck chemicals was collected between March 2010 and January 2013, from consecutive patients admitted for DU bleeding who had endoscopic, angiographic or surgical management. All patients had surveillance endoscopy after 4 or more weeks of PPI therapy. Patient demographics, location and morphology of ulcers, types of intervention and treatment, and co-morbidities were analyzed. The main outcome variables were ulcer healing and clinical predictors of ulcer persistence. Results: 421 patients presented with acute DU bleeding during the study period, of which 77 met study criteria and were analysed; 47 males, 30 females. Mean age was 66.4 years; range 18–88.

Therefore, we investigated the patients with repeated overt OGIB in terms of clinical data and medication. Methods: We retrospectively reviewed the clinical records of 81 patients, who referred to our hospital due to overt OGIB between January 2011 and June 2014. Results: Fifteen (18.5%; 11 men, 4 women, mean age 70.2 ± 10.2 years) of 81 patients had repeated overt OGIB. Small intestinal lesions were detected in 11 patients (73.3%) by DBE. Hemostatic therapy was performed in 6 (54.5%) of those patients. However, rebleeding was occurred in five (83.3%) of

six patients with hemostatic therapy. Underlying illness of 15 patients were as follows; 3 cases of heart valve disease (20%), 8 cases of heart disorder (13.3%), 2 cases of abdominal aortic aneurysm (13.3%), 4 cases of chronic TSA HDAC mouse renal failure (26.7%), 3 cases of dialysis treatment (20%). Oral medications were as follows: 6 anticoagulant drug (40%), 2 low dose aspirin (13.3%), 1 antiplatelet drug (6.7%). Twelve (80%) patients with repeated overt OGIB received transfusion. The rate of transfusion was significantly higher in patients with repeated overt OGIB when compared with patients with single overt OGIB (p < 0.05). Conclusion: Anticoagulant

ACP-196 may be the risk for repeated overt OGIB, and the patients with repeated overt OGIB tend to have severe bleeding. Key Word(s): 1. obscure gastrointestinal bleeding; 2. rebleeding Presenting Author: BOON EU ANDREW KWEK Additional Authors: TECK KIANG MALCOLM TAN, TIING LEONG ANG, ENG KIONG TEO, KWONG MING FOCK Corresponding Author: BOON EU ANDREW KWEK Affiliations: Changi General Hospital, Changi General Hospital, Changi General Hospital, Changi General Hospital Objective: Surveillance endoscopy is performed to confirm ulcer healing and absence of cancer in patients with gastric ulcer. Although not routine in patients with simple duodenal ulcers (DU), endoscopy may be repeated in patients with complicated

ulcers to ensure adequate healing prior to commencing anti-thrombotic agents or discontinuing proton pump inhibitor (PPI). We aimed to determine the healing rate of complicated DUs, predictors of delayed healing and the clinical impact of surveillance endoscopy in these patients. Methods: Data selleck chemical was collected between March 2010 and January 2013, from consecutive patients admitted for DU bleeding who had endoscopic, angiographic or surgical management. All patients had surveillance endoscopy after 4 or more weeks of PPI therapy. Patient demographics, location and morphology of ulcers, types of intervention and treatment, and co-morbidities were analyzed. The main outcome variables were ulcer healing and clinical predictors of ulcer persistence. Results: 421 patients presented with acute DU bleeding during the study period, of which 77 met study criteria and were analysed; 47 males, 30 females. Mean age was 66.4 years; range 18–88.

The correlation between EGFR and mig-6 was analyzed by comparing the expression values of both proteins in each tumor directly and calculated using the Spearman’s rank test. P values were calculated using the two-sided Fisher’s exact test or the paired Student t test, and P < 0.05 was considered statistically significant. The statistical analysis

was performed with the SPSS 12.0 software (SPSS Inc., Chicago, IL). We have reported that mig-6 knockout mice display multiple phenotypes in various organs.14 selleck chemicals llc Interestingly, mig-6 deficiency led to a distinct increase in EGFR protein levels in the livers of 2- and 5-week-old knockout mice, suggesting a liver-specific role for mig-6 in the regulation of EGFR protein stability and possibly function (Fig. 1A ). In order to investigate a possible function of mig-6 in the liver, we isolated click here primary hepatocytes from adult mig-6 knockout and wild-type animals. Mig-6–deficient hepatocytes retained somewhat higher levels of basal EGFR, AKT, and extracellular-regulated kinase 1/2 (ERK1/2) phosphorylation compared with wild-type controls, even in the absence of EGF stimulation, suggesting

that loss of mig-6 is sufficient to generate some constitutive EGFR activation (Fig. 1B). Upon EGF stimulation, mig-6–deficient hepatocytes showed an increase in EGFR phosphorylation and sustained activation of AKT (Fig. 1B). In contrast, ERK1/2 activation remained comparable between wild-type and knockout cells, suggesting that loss of mig-6 leads to an up-regulation of the EGFR/phosphoinositol learn more 3-kinase/AKT pathway. Based on our observations in isolated primary hepatocytes, we wanted to study the effect of mig-6 deficiency on hepatocyte proliferation in vivo. Therefore, we subjected mig-6 knockout and wild-type control mice to a 70% PH and monitored liver regeneration. In agreement with published data,16, 17 mig-6 expression levels were found

to be up-regulated in wild-type mice after PH (Fig. 2A ). Interestingly, mig-6 knockout mice displayed an increase in hepatocytes re-entering the cell cycle between 24 and 36 hours after PH (Fig. 2B,C). In contrast, only a few wild-type hepatocytes were able to enter S-phase at these time points. Similar to wild-type mice, the percentage of proliferating hepatocytes in mig-6 knockout livers reached a maximum at 48 hours and declined thereafter (Fig. 2B,C), suggesting that mig-6 exerts its function in the initial phases of liver regeneration. In order to dissect the signaling mechanisms underlying the early hepatocyte proliferation in regenerating mig-6 knockout livers, we analyzed components of the EGFR signaling pathway.

The correlation between EGFR and mig-6 was analyzed by comparing the expression values of both proteins in each tumor directly and calculated using the Spearman’s rank test. P values were calculated using the two-sided Fisher’s exact test or the paired Student t test, and P < 0.05 was considered statistically significant. The statistical analysis

was performed with the SPSS 12.0 software (SPSS Inc., Chicago, IL). We have reported that mig-6 knockout mice display multiple phenotypes in various organs.14 click here Interestingly, mig-6 deficiency led to a distinct increase in EGFR protein levels in the livers of 2- and 5-week-old knockout mice, suggesting a liver-specific role for mig-6 in the regulation of EGFR protein stability and possibly function (Fig. 1A ). In order to investigate a possible function of mig-6 in the liver, we isolated CHIR-99021 ic50 primary hepatocytes from adult mig-6 knockout and wild-type animals. Mig-6–deficient hepatocytes retained somewhat higher levels of basal EGFR, AKT, and extracellular-regulated kinase 1/2 (ERK1/2) phosphorylation compared with wild-type controls, even in the absence of EGF stimulation, suggesting

that loss of mig-6 is sufficient to generate some constitutive EGFR activation (Fig. 1B). Upon EGF stimulation, mig-6–deficient hepatocytes showed an increase in EGFR phosphorylation and sustained activation of AKT (Fig. 1B). In contrast, ERK1/2 activation remained comparable between wild-type and knockout cells, suggesting that loss of mig-6 leads to an up-regulation of the EGFR/phosphoinositol selleck compound 3-kinase/AKT pathway. Based on our observations in isolated primary hepatocytes, we wanted to study the effect of mig-6 deficiency on hepatocyte proliferation in vivo. Therefore, we subjected mig-6 knockout and wild-type control mice to a 70% PH and monitored liver regeneration. In agreement with published data,16, 17 mig-6 expression levels were found

to be up-regulated in wild-type mice after PH (Fig. 2A ). Interestingly, mig-6 knockout mice displayed an increase in hepatocytes re-entering the cell cycle between 24 and 36 hours after PH (Fig. 2B,C). In contrast, only a few wild-type hepatocytes were able to enter S-phase at these time points. Similar to wild-type mice, the percentage of proliferating hepatocytes in mig-6 knockout livers reached a maximum at 48 hours and declined thereafter (Fig. 2B,C), suggesting that mig-6 exerts its function in the initial phases of liver regeneration. In order to dissect the signaling mechanisms underlying the early hepatocyte proliferation in regenerating mig-6 knockout livers, we analyzed components of the EGFR signaling pathway.

The correlation between EGFR and mig-6 was analyzed by comparing the expression values of both proteins in each tumor directly and calculated using the Spearman’s rank test. P values were calculated using the two-sided Fisher’s exact test or the paired Student t test, and P < 0.05 was considered statistically significant. The statistical analysis

was performed with the SPSS 12.0 software (SPSS Inc., Chicago, IL). We have reported that mig-6 knockout mice display multiple phenotypes in various organs.14 selleck chemical Interestingly, mig-6 deficiency led to a distinct increase in EGFR protein levels in the livers of 2- and 5-week-old knockout mice, suggesting a liver-specific role for mig-6 in the regulation of EGFR protein stability and possibly function (Fig. 1A ). In order to investigate a possible function of mig-6 in the liver, we isolated selleck chemicals llc primary hepatocytes from adult mig-6 knockout and wild-type animals. Mig-6–deficient hepatocytes retained somewhat higher levels of basal EGFR, AKT, and extracellular-regulated kinase 1/2 (ERK1/2) phosphorylation compared with wild-type controls, even in the absence of EGF stimulation, suggesting

that loss of mig-6 is sufficient to generate some constitutive EGFR activation (Fig. 1B). Upon EGF stimulation, mig-6–deficient hepatocytes showed an increase in EGFR phosphorylation and sustained activation of AKT (Fig. 1B). In contrast, ERK1/2 activation remained comparable between wild-type and knockout cells, suggesting that loss of mig-6 leads to an up-regulation of the EGFR/phosphoinositol this website 3-kinase/AKT pathway. Based on our observations in isolated primary hepatocytes, we wanted to study the effect of mig-6 deficiency on hepatocyte proliferation in vivo. Therefore, we subjected mig-6 knockout and wild-type control mice to a 70% PH and monitored liver regeneration. In agreement with published data,16, 17 mig-6 expression levels were found

to be up-regulated in wild-type mice after PH (Fig. 2A ). Interestingly, mig-6 knockout mice displayed an increase in hepatocytes re-entering the cell cycle between 24 and 36 hours after PH (Fig. 2B,C). In contrast, only a few wild-type hepatocytes were able to enter S-phase at these time points. Similar to wild-type mice, the percentage of proliferating hepatocytes in mig-6 knockout livers reached a maximum at 48 hours and declined thereafter (Fig. 2B,C), suggesting that mig-6 exerts its function in the initial phases of liver regeneration. In order to dissect the signaling mechanisms underlying the early hepatocyte proliferation in regenerating mig-6 knockout livers, we analyzed components of the EGFR signaling pathway.

, 1996) with

a readily available, evenly distributed and relatively stable food source (Dostine & Franklin, 2002), all of which could presumably reduce extrinsic mortality. In our comprehensive multivariate analysis, breeding sociality significantly affected mean maximum longevities of avian families (Table 2; Appendix 3). A posteriori analyses revealed that social species lived longer than non-social species (Fig. 4). These results agree with those of Arnold & Owens (1998), who reported that cooperative breeding was correlated with low annual mortality and long life spans, as predicted by kin selection PLX4032 purchase theory and life-history theory (Bourke, 2007). However, subsequent analyses by Møller (2006) and Blumstein & Møller (2008) called into question the role of sociality in the evolution of this website avian longevities and senescence patterns. The reasons for the difference between our results and theirs probably lie in differences

in both sample sizes and definitions of sociality. Whereas Møller (2006) defined sociality as ‘colonial nesting’ and Blumstein & Møller (2008) defined it as ‘cooperative breeding,’ our definition included both. We took the broader approach because both colonial nesting and cooperative breeding have often been linked to reduced predation rates on adult birds, chicks and eggs, due to shared vigilance, sentinels, alarm calling, cooperative group defense, safety in numbers and selfish herd effects (e.g. Hoogland & Sherman, 1976; Hoogland, 1981; Hailman, McGowan & Woolfenden, 1994; Clutton-Brock et al., 1999; Hatchwell

& Komdeur, 2000; reviewed by Safran et al., 2007). The link between sociality and longevity is illustrated by the characteristics of the four longest and shortest-lived avian orders learn more (Fig. 1). All four species of Phoenicopteriformes (flamingos) in our data base (Appendix 2) breed in colonies and crèche their chicks, all 25 Procellariiformes (petrels and shearwaters) and all 16 Pelecaniformes (pelicans) nest colonially, and 25 of 47 species (54%) of Psittaciformes (parrots) nest colonially or breed cooperatively. By contrast, only 38 of 179 (21%) Passeriformes (perching birds) and only two of nine (22%) Columbiformes (pigeons) in our data base nest colonially or breed cooperatively, only one of four (25%) Podicipediformes (grebes) breeds colonially, and only three of 15 (20%) Piciformes (woodpeckers) breed cooperatively.

, 1996) with

a readily available, evenly distributed and relatively stable food source (Dostine & Franklin, 2002), all of which could presumably reduce extrinsic mortality. In our comprehensive multivariate analysis, breeding sociality significantly affected mean maximum longevities of avian families (Table 2; Appendix 3). A posteriori analyses revealed that social species lived longer than non-social species (Fig. 4). These results agree with those of Arnold & Owens (1998), who reported that cooperative breeding was correlated with low annual mortality and long life spans, as predicted by kin selection MK-2206 mouse theory and life-history theory (Bourke, 2007). However, subsequent analyses by Møller (2006) and Blumstein & Møller (2008) called into question the role of sociality in the evolution of Inhibitor Library purchase avian longevities and senescence patterns. The reasons for the difference between our results and theirs probably lie in differences

in both sample sizes and definitions of sociality. Whereas Møller (2006) defined sociality as ‘colonial nesting’ and Blumstein & Møller (2008) defined it as ‘cooperative breeding,’ our definition included both. We took the broader approach because both colonial nesting and cooperative breeding have often been linked to reduced predation rates on adult birds, chicks and eggs, due to shared vigilance, sentinels, alarm calling, cooperative group defense, safety in numbers and selfish herd effects (e.g. Hoogland & Sherman, 1976; Hoogland, 1981; Hailman, McGowan & Woolfenden, 1994; Clutton-Brock et al., 1999; Hatchwell

& Komdeur, 2000; reviewed by Safran et al., 2007). The link between sociality and longevity is illustrated by the characteristics of the four longest and shortest-lived avian orders check details (Fig. 1). All four species of Phoenicopteriformes (flamingos) in our data base (Appendix 2) breed in colonies and crèche their chicks, all 25 Procellariiformes (petrels and shearwaters) and all 16 Pelecaniformes (pelicans) nest colonially, and 25 of 47 species (54%) of Psittaciformes (parrots) nest colonially or breed cooperatively. By contrast, only 38 of 179 (21%) Passeriformes (perching birds) and only two of nine (22%) Columbiformes (pigeons) in our data base nest colonially or breed cooperatively, only one of four (25%) Podicipediformes (grebes) breeds colonially, and only three of 15 (20%) Piciformes (woodpeckers) breed cooperatively.

6). However, in luciferase reporter and xenograft data, it seems that SOX1 could antagonize the Wnt pathway independent of the CTNNB1 mutation. selleck screening library Furthermore, luciferase reporter analysis of mutant SOX1 (with a C terminus truncated region) indicated that they failed to suppress the β-catenin/TCF-dependent transcriptional activity (Supporting Fig. 7). Our data showed that the high-mobility group domain (but not the C terminus)

is essential for SOX1 to suppress β-catenin-mediated TCF/LEF signaling. Kan et al.26 showed that SOX1 could bind to β-catenin, and the C terminus of SOX1 is required for this interaction. Transcriptional regulators of SOX proteins generally require the cooperation of partner factors for the regulation of specific target genes in a cell type-specific fashion.37, 38 Although an authentic BIBW2992 partner protein associated with SOX1 was not identified, the possible explanation for the conflicting results may result from the putative partner protein influences on the interaction of SOX1 and β-catenin in different cell contexts. Moreover, Mathews et al.18 found that SOX1 promoted invasion of prostate cancers through interaction

with STAT3, increasing the IL-6/STAT3 pathway activity. They did not investigate the relationship between SOX1 and Wnt signaling. It has been reported that SOX proteins can play either a tumor suppressor or an oncogenic role owing to variations in the genetic background, signaling network, and cellular context. The controversial results may arise from the property of SOX proteins as transcription factors. Moreover, we demonstrated that decreased protein levels of c-MYC and cyclin D1 and increased protein levels of p21 and p27 were associated with overexpression of SOX1 in Hep3B cells. In addition, deprivation of SOX1 expression restored find more the expression levels of both c-MYC and cyclin D1. These results suggest that SOX1 inhibited Wnt signaling and then decreased β-catenin/TCF downstream genes. It has been reported that c-MYC may repress p21 expression through different mechanisms.39,

40 Moreover, van de Wetering et al.41 found that the decreased expression of c-MYC releases p21 (CIP1/WAF1) transcription after disruption of β-catenin/TCF-4 activity, which in turn mediates G1 arrest and differentiation. This master switch mediated by the β-catenin/TCF complex controls proliferation versus differentiation in healthy and malignant intestinal epithelial cells. From our present data, we also found that restoration of SOX1 decreased c-MYC but increased p21 expression. Whether decreased c-MYC can release p21 or whether SOX1 directly regulates the p21 expression still needs further investigation. Furthermore, SOX2 interacts with β-catenin in osteoblasts and inhibits the Wnt-responsive reporter assay in HEK293 cells,36 and plays important roles in growth inhibition through interfering with Wnt signals by downregulation of cyclin D1 and upregulation of p27kip1 level in gastric cancers.