Changes in expression of some apoptotic markers in different types of human endometrium

The maintenance of tissue homeostasis and highly balanced counteraction of cellular proliferation and apoptosis are essential for tissue integrity. In our study, we evaluated the expression of apoptosis- regulating proteins Bcl-2, Bax and PARP, and executive apoptotic enzyme caspase-3 in normal, atrophic, hyperplastic and cancerous endometrium. Endometrial samples were obtained from patients who underwent curettage, hysteroresection or hysterectomy. The protein levels were quantified by immunoblotting. We observed a higher level of important apoptotic enzyme pro-caspase-3 and its active form in hyperplastic and cancerous endometrium, when compared to normal endometrium. The value of Bcl-2/Bax ratio, which reflects cellular resistance to apoptosis, was determined as > 1 for cancerous, normal, and atrophic endometrium. Thus, the effort to eliminate pre-neoplastic and neoplastic cells by apoptosis indicated by high pro-caspase-3 and caspase-3 levels seems to be overcome by a greater proliferative adjustment suggested by higher Bcl-2/Bax ratios in the samples examined. The PARP levels did not vary significantly among the groups. The levels of all examined proteins were significantly lower in atrophic endometrium. Our results suggest that pre-neoplastic and neoplastic states of human endometrium are not influenced simply by changes in apoptosis, but may also be affected by cellular proliferation. A high Bcl-2/Bax ratio as observed in cancerous endometrium can point to deregulation of apoptotic programmes. Thus, the onset and progression of endometrial malignancy could be linked to increased cellular proliferation with defects in apoptotic control.