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pubmed:abstractText |
Cancer cells undergo multi-step processes in obtaining the ability to metastasize, and are constantly exposed to signals that induce apoptosis. Acquisition of anti-apoptotic properties by cancer cells is important for metastasis, and recent studies suggest that transforming growth factor (TGF)-? promotes the survival of certain types of cancer cells. Here, we found that in highly metastatic breast cancer cells, JygMC(A), JygMC(B) and 4T1, TGF-? ligands were produced in autocrine fashion. Pharmacological inhibition of endogenous TGF-? signalling by a TGF-? type I receptor kinase inhibitor in serum-free conditions increased the expression of BH3-only protein, Bim (also known as Bcl2-like 11) in JygMC(A) and JygMC(B) cells, and caused apoptotic cell death. We also found that induction of Bim by TGF-? was not observed in Foxc1 knocked-down cancer cells. These findings suggest that TGF-? plays a crucial role in the regulation of survival of certain types of cancer cells through the TGF-?-Foxc1-Bim pathway, and that specific inhibitors of TGF-? signalling might be useful as apoptosis inducers in breast cancer cells.
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pubmed:affiliation |
Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
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