Inhibition of c-Myc Induced Apoptosis by Focal Adhesion Kinase, PP125FAK, in Mammary Carcinoma Cells

摘要

The purpose of the research described in this proposal is to identify and characterize the role of adhesion and ppl25(FAK) in the survival of breast cancer cells expressing c-Myc. This work utilizes a breast cancer cell line Myc83 obtained from transgenic mice overexpressing c-myc. These cells undergo a rapid apoptotic cell death upon removal of EGF. The major findings of this work to date are that type IV collagen promotes the survival of Myc83 cells in the absence of EGF. Adhesion based survival is mediated by the beta 1 integrin, in that inhibition of the beta 1 integrin using neutralizing antibodies promotes the rapid apoptotic cell death of Myc83 cells. We have also determined that collagen IV does not stimulate the growth of Myc83 cells and does not change their cell cycle. Inhibitors of actin polymerization promote the apoptosis of Myc83 cells. Lastly, growth of Myc83 cells on collagen IV slightly increases the expression of the cell death inhibitor Bcl-2 and that inhibition of collagen IV adhesion by neutralizing antibodies to beta 1 integrins increased expression of the cell death inducer Bax. These results strongly suggest that collagen IV functions as a survival factor for Myc-83 cells and that this activity is mediated by beta 1 integrins.