Knockdown of PINCH-1 protein sensitizes the estrogen positive breast cancer cells to chemotherapy induced apoptosis.

INTRODUCTION: PINCH-1 is a ubiquitously expressed protein belonging to the focal adhesion protein group which has a role in cell survival, spreading, adhesion and migration. It has been implicated in pathogenesis of several cancers. In the present study we aimed to investigate the role of this protein in estrogen positive and negative breast cancer subtypes.

MATERIALS AND METHODS: PINCH-1 expression was studied in two estrogen positive(T47D and MCF-7) and one estrogen negative cell lines before and after treatment with six drugs (Cyclophosphamide, Celecoxib, Doxorubicin, Paclitaxel, Etoposide and Tamoxifen). Then the protein was knocked down using siRNA against PINCH-1 and change in percentage of apoptotic cells was analysed by flow cytometry.

RESULTS: We observed increased but differential expression of PINCH-1 in the three breast cancer cell lines with a higher expression in estrogen positive cell lines. Knocking down of PINCH-1 led to a significant (p-value<0.05) enhancement in apoptosis in T47D cells in response to 4/6 (cyclophosphamide, celecoxib, paclitaxel, doxorubicin) drugs. Though an increase in apoptosis was observed in MCF-7 cells also, it was not found to be significant.The MDA-MB-231 cells however, did not show significant apoptosis upon PINCH-1 knockdown.

CONCLUSION: The results suggest that PINCH-1 may be playing an important role in etiopathogenesis of both subtypes breast cancer. However, enhanced apoptosis observed only in estrogen positive and not in estrogen negative cells upon PINCH-1 knockdown point towards participation of some other protein with redundant functions in the later subtype which needs to be investigated.