Prognostic significance of apoptosis regulators in breast cancer

Dysregulation of normal programmed cell death mechanisms plays an important role in the pathogenesis and progression of breast cancer, as well as in r esponses of tumors to therapeutic intervention. Overexpression of anti-apop totic members of the Bcl-2 family such as Bcl-2 and Bcl-x(L) has been impli cated in cancer chemoresistance, whereas high levels of pro-apoptotic prote ins such as Bar promote apoptosis and sensitize tumor cells to various anti cancer therapies. Though the mechanisms by which Bcl-2 family proteins regu late apoptosis are diverse, ultimately they govern decision steps that dete rmine whether certain caspase family cell death proteases remain quiescent or become active. To date, approximately 17 cellular homologs of Bcl-2 and at least 15 caspases have been identified in mammals. Other types of protei ns may also modulate apoptotic responses through effects on apoptosis-regul atory proteins, such as BAG-1 - a heat shock protein 70 kDa (Hsp70/Hsc-70)- binding protein that can modulate stress responses and alter the functions of a variety of proteins involved in cell death and division. In this repor t, we summarize our attempts thus far to explore the expression of several Bcl-2 family proteins, caspase-3, and BAG-1 in primary breast cancer specim ens and breast cancer cell lines. Moreover, we describe some of our prelimi nary observations concerning the prognostic significance of these apoptosis regulatory proteins in breast cancer patients, contrasting results derived from women with localized disease (with or without node involvement) and m etastatic cancer.