Overexpression and cytoplasmic localization of caspase-6 is associated with lamin A degradation in set of ovarian cancers

BackgroundIn most women with ovarian cancer, the diagnosis occurs after dissemination of tumor cells beyond ovaries. Several molecular perturbations occur ahead of tumor initiation including loss of lamin A/C. Our hypothesis was that the loss of nuclear structural proteins A type lamins (lamin A/C) transcribed from LMNA gene and substrate for active caspase-6 maybe one of the molecular perturbations. Our objective is to investigate the association between the loss of lamin A/C and the overexpression of caspase-6 in ovarian cancer cells.MethodWestern blotting and immunofluorescence were used to analyze the expression of lamin A/C and active caspase-6 in normal human ovarian surface epithelial (HOSE) cells, immortalized human ovarian surface epithelial cells and a set of seven ovarian cancer cell lines (including OVCAR3, OVCAR5, and A2780). The activity of caspase-6 was measured by densitometry, fluorescence and flow cytometry. Immunohistochemistry was used to evaluate the expression of caspase-6 in set of ovarian cancer tissues previously reported to have lost lamin A/C.ResultsThe results showed that HOSE cells expressed lamin A/C and no or low level of active caspase-6 while cancer cells highly expressed caspase-6 and no or low level of lamin A/C. The inhibition of caspase-6 activity in OVCAR3 cells increased lamin A but has no effect on lamin C; active caspase-6 was localized in the cytoplasm associated with the loss of lamin A.ConclusionOverexpression and cytoplasmic localization of caspase-6 in ovarian cancer cells may be involved in lamin A degradation and deficiency observed in some ovarian cancer cells.