Science et thérapie du cancer

Sensitising Breast Cancer Cells to Chemotherapy by Down Regulation of Lifeguard

Abstract

Anna-Lena Gratzke, Kerstin Reimers, Peter M Vogt and Vesna Bucan

Introduction: Lifeguard (LFG) is an anti-apoptotic protein that inhibits programmed cell death mediated by Fas in tumour cells. The exact mechanism of action and the molecular function from LFG in the carcinogenesis of human breast cells is not clear. But the expression of LFG mRNA correlates with LEF-1 transcription factor activity.

Methods: In the present study, chemotherapeutic-induced apoptotic effects were studied using MCF-7 cells as an in vitro test model. Molecular (Western blot and RT-PCR) techniques were used to investigate LFG expression. To investigate the breast cancer cell proliferation in presence of siRNA-LFG we performed fluorescent cell viability assays.

Results: The results indicated that, a decrease of LFG expression using siRNA correlates with an increased sensitivity to Trastzumab and Erlotinib. Moreover, cell cycle analysis of LEF-1 siRNA-transfected human breast cancer cells revealed a significant arrest in G2 phase.

Conclusion: Taken together, our results indicate a pivotal role of LFG in the regulation of apoptosis in MCF-7 breast cancer cells.