BCL‐6 Prevents Mammary Epithelial Apoptosis, Promotes Cell Survival and is Expressed in Breast Carcinoma

Alenzi, F. Q. B.

Background: Proliferation, differentiation and apoptosis are essential processes in the normal functions of the mammary epithelium. The hypothesis examined in this study is that the transcription factor BCL‐6 is critically important not only for regulating B‐cell growth and development but also for mammary epithelial apoptosis. Methodology: Twenty breast cancer cases and 31 healthy controls were used to investigate whether BCL‐6 protein in involved in breast cancer (grade III). Full length BCL‐6 cDNA was retrovirally transduced into EpH‐4 cell line. We then used flow cytometry of BrdUrd‐stained cells to investigate the cell‐cycle duration of the control and transduced cell lines. TUNEL was used as a marker of apoptosis to find out differences in the frequencies of apoptotic cells in the control and transduced cell lines. Finally, immunohistochemistry staining was performed to detect BCL‐6 in breast cancer (III). Results: Restoration of BCL‐6 into EpH‐4 cells not only inhibits apoptosis but also prolongs the cell cycle and results in increased cell size and protein content. The results also indicated that the cell‐cycle time of BCL‐6‐transduced EpH‐4 cells is prolonged by about 3 h, presumably as a result of the action of BCL‐6 at the BCL‐6 at the G1/S transition. We found differences in the frequencies of viable and apoptotic cells in cultures of the parent EpH‐4 cells, control‐transduced EpH‐4 cells and BCL‐6‐transduced EpH‐4 cells. Consistently, we demonstrated that BCL‐6 is expressed in 90% of high grade of breast carcinoma, which is considered as the most aggressive of tumours. Conclusion: Together, these results suggest that BCL‐6 is likely to be involved in mammary gland development and carcinogenesis.