Study About Taxol Resistance And Cell Differention

part Ⅰ:Taxol was originally isolated from Taxul brevifolia. The subsequent in vitro and in vivo studies have demonstrated that taxol is able to interact with β-tubulin.and promote tubulin polymerization, therefore leading to G2/M arrest by abnormal mitotic spindle formation and subsequent cell death by apoptosis. Given the potent ability to induce cell cycle arrest and apoptosis, taxol has been widely used in cancer chemotherapy to treat many malignancies including lung, ovarian, breast cancer, head and neck cancers.Unfortunately, the efficacy of taxol therapy is greatly limited by the development of taxol resistance. To identify novel mechanism(s) of acquired resistance to taxol, we generated one taxol-resistant cell line TRC30by chronic exposure of ovarian cancer cell line HeLa to taxol. Here we report TNFAIP1(tumor necrosis factor alpha inducing protein1) as a novel taxol resistance-associated gene. TNFAIP1is highly upregulated in taxol-resistant TRC30cells. Increased expression of TNFAIP1is shown to confer acquired taxol resistance. Mechanistically, TNFAIP1competes with taxol for binding to β-tubulin, thereby antagonizing taxol-induced tubulin polymerization. We also show that TNFAIP1expression is controlled by the transcriptional factor Sp1in response to taxol treatment. Collectively, these data uncover a novel mechanism of taxol resistance where Spl-mediated upregulation of TNFAIP1contributes to acquired resistance to taxol, and suggest that Spl-TNFAIP1axis, particularly TNFAIP1, may represent as a novel therapeutic target for the treatment of cancer.partⅡ:Cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type during proliferation. Differentiation occurs not only during embryonic development, but also in adults to replace the senescent and dead cells. Using shRNA library as screen methods, we have already found Urdpl, which influence stem cell maintainess and differentiation based on stem cell marker detection in R1cells. In order to study the underlying molecular mechanism, we are planning to search for their interacting proteins through pull down and immunoprecipitation. We will also clarify the role Urdpl play in committed differentiation using Teratoma and EB formation.