Abstract# 1952: Down regulation of myeloid cell leukemia 1 through inhibiting Erk/Pin 1 pathway by sorafenib facilitates chemosensitization in breast cancer

Myeloid cell leukemia-1 (Mcl-1), a Bcl-2-like antiapoptoticprotein, is overexpressed in a number of human tumor cells including breast cancer, pancreatic cancer, hepatocellular carcinoma, melanoma, leukemia etc. and plays a role in cell immortalization and chemoresistancein these malignancies. The short half-life (~30 to 120min) of Mcl-1 suggests its highly post-translational regulation in cells. GSK-3\#946; is known to phosphorylate Mcl-1 to promote its ubiquitination by \#946;-Trcp and degradation. However, it is far from clear how Mcl-1is stabilized in cancer cells. In addition, Erk activation can up-regulate Mcl-1, but the mechanism still remains to be elucidated. A peptidyl-prolyl cis/transisomerase, Pin1 is involved in many cellular events, such ascell cycle progression, cell proliferation, and differentiationthrough isomerizing prophosphorylated substrates. It has beenreported that down-regulation of Pin1 induces …