Different expression patterns of Bcl-2 family genes in breast cancer by estrogen receptor status with special reference to pro-apoptotic Bak gene

Oncogenic and anti-apoptotic Bcl-2 is expressed much less in estrogen recep tor alpha (ER alpha) negative breast cancers, which show more malignant phe notypes, than ER alpha-positive, indicating that some other Bcl-2 family me mber(s) are involved in the apoptotic balance of the cancer cells. We first analyzed mRNA expression of pro-apoptotic Bak and Bar along with that of a nti-apoptotic Bcl-2 and Bcl-x(L), using breast cancer specimens of 27 patie nts. Bak mRNA was expressed much less in ER alpha negative breast cancers, along with reduced expression of Bcl-2, Immunostaining of sections of 108 p atients confirmed the observation. Next, stable transformants of MCF-7 cell s with sense Bak expression Vector showed fewer colonies in soft agar compa red with the parental cells, while stable introduction of antisense Bak vec tor enhanced colony formation at lower estradiol concentrations. The reduct ion of Bak may play important roles in malignant development of breast canc er to acquire estrogen independency, counteracting the reduced Bcl-2.