The cell lines provide a framework for comparative molecu CC 5013 lar genetic studies investigating the genomic landscape by gene expression, copy number variation or mutation analysis. The unique phenotypes exhibited by the cell lines suggest that they reflect the complexity of ovarian cancer disease. The paired sample cell line model from patient 2295, will allow for further discrimination of acquired resistance, affected by the chemotherapy re gime. Although cell lines from patient 1369 and 3133 do not show signs of acquired resistance, both offer avenues of research into tumor evolution. Specifically, further study of the1369 cell lines would allow for the under standing of the molecular basis for the high innate re sistance to both carboplatin and paclitaxel.

In 3133, three distinct time points are represented offering pos sible insights into the mechanisms of tumor progression and evolution. Background The S100 protein family, consisting of over 20 members, constitutes Inhibitors,Modulators,Libraries the largest subgroup of calcium binding pro teins. These proteins share amino acid sequence similar ity as well as the functional EF hand structure motif, which plays a key role in calcium binding through a helix loop helix topology. Proteins containing this motif are involved in virtually all normal and pathological cell functions including gene transcription, inflammatory and immune responses, regulation of protein phosphor Inhibitors,Modulators,Libraries ylation, transcription factors, anti microbial responses, Ca2 homeostasis, the dynamics of Inhibitors,Modulators,Libraries cytoskeleton consti tuents, as well as cell proliferation, differentiation, and death.

Given the global importance of these pro teins, inhibitors of Inhibitors,Modulators,Libraries specific S100 proteins Inhibitors,Modulators,Libraries are currently being developed as therapeutics for diseases including diabetes mellitus, heart failure, neurological diseases, and several types of cancer. The role of S100 protein in breast cancer is only begin ning to emerge. A recent observational study demonstrated upregulation of S100A1, S100A2, S100A4, S100A6, S100A8, S100A9, S100A10, S100A11, and S100A14 in basal type breast cancers compared to non basal types. In the same study, it was determined that expression of S100A8 and S100A9 were elevated in high grade com pared to low grade tumors and estrogen receptor negative tumors compared to ER positive tumors.

Mechanistic studies demonstrated that overexpression of S100A4 induced metastatic capability in non metastatic breast cancer cells and stimulated metastasis of benign tumors in transgenic mouse model systems. S100A7 was shown promotion info to be upregulated in high grade ductal car cinoma in situ, and is correlated with poor prognosis in estrogen negative breast cancer. In vitro, S100A7 overex pression increased breast cancer cell growth, invasive ness, and increased tumorigenicity in a xenograft mouse model.