Significance of Bcl-2 Family Members in Breast Carcinogenesis

The most common cancer among women globally is breast cancer with incidence rate highest in Asia and Europe and is the most common cancer maladies in women of India. Apoptosis is central to maintaining cellular homeostasis but a defect in its machinery or unwarranted expression can lead to cellular mayhem. Evasion of cancer and aberrant expression of anti-apoptotic factors are critical hallmarks of cancer. Bcl-2 family members are anti-apoptotic and contributes significantly to breast cancer survival and treatment resistance. Primary breast tumor tissues and adjacent normal breast samples were obtained from 100 breast cancer patients undergoing surgery at Regional Cancer Centre, Thiruvananthapuram, Kerala, India. A slightly enhanced expression of Bcl-2 at the mRNA level was observed in tumor samples compared to normal breast samples. Conversely, the protein expression of Bcl-2 and its family members such as Bcl-xL and Mcl-1 showed a drastic increase in tumor samples. Immunohistochemistry analyses revealed a strong cytoplasmic expression of Bcl-2 in tumor tissues whereas Bcl-xL and Mcl-1 mostly showed moderate cytoplasmic immunostaining pattern. We observed that only 10% of the normal samples showed strong cytoplasmic staining for Bcl-2 whereas weak cytoplasmic expression for Bcl-xL and Mcl-1 was observed in majority of the normal samples. Spearman correlation analyses revealed a strong association of Bcl-2 with Bcl-xL and Mcl-1 in tumor samples and normal tissues. The protein expression of Bcl-xL showed robust association with clinicopathological features of breast cancer patients such as tumor size and parity and significant association between Bcl-2 and menopausal status. This study indicates that development of inhibitors against Bcl-2 family members may improve the treatment outcome of breast cancer patients.