The role of glucose regulated protein (GRP)-78 in regulating cell growth and apoptosis in human breast and ovarian cancer cells

Abstract

Objective: To investigate the role of GRP78 in regulating cell growth and apoptosis in human breast and ovarian cancer cells and examine whether overexpression of GRP78 protects cells from endoplasmic reticulum (ER) stress and chemotherapeutic drug induced apoptosis. Methods: GRP78 expression was measured by Western blot and immunofluorescent microscopy. Cell cycle analyses and cell proliferation were examined by flow cytometry and MTT assay, respectively. Apoptosis was determined by DAPI and TUNEL staining. Results: Overexpression of GRP78 in both breast and ovarian cancer cells led to increases in cell growth, which was due to decreased apoptosis. Treatment with tunicamycin and 2-deoxyglucose induced an increase in GRP78 expression, suggesting that GRP78 overexpression may alleviate unfolded protein stress in the ER. We also showed that overexpression of GRP78 protected both breast and ovarian cancer cells against apoptosis induced by chemotherapeutic drugs such as paclitaxel. Conclusions: Upregulation of GRP78 is one of the mechanisms which may enhance survival and drug resistance of breast and ovarian cancer cells.