Poly(ADP-ribose) polymerase-1, a novel partner of progesterone receptors in endometrial cancer and its precursors

Endometrial carcinomas are the most common malignancy of the female genital tract. Although the downregulation of the progesterone receptor (PR) in the progression of endometrioid carcinomas (ECs) has been well documented, the mechanism of PR alteration in endometrioid carcinogenesis is poorly understood. Recently, biochemical studies have shown that the DNA strand break-sensing molecule poly(ADP-ribose) polymerase (PARP-1) was associated with the DNA binding domain of PR. In our present study, we show that in normal endometrial epithelium, the expression level of PARP-1 protein is high in the proliferative phase but markedly decreases during the secretory phase. Interestingly, PARP-1 expression gradually increases in nonatypical and atypical endometrial hyperplasia, reaching its highest level in grade I, and decreases significantly toward grade III ECs. Notably, PARP-1 and PR expressions, in each stage, are positively correlated (p < 0.0001), with the exception of nonendometrioid carcinomas. Thus, these data suggest that PARP-1 is substantially involved in the regulation of progesterone action in the development of ECs. © 2004 Wiley-Liss, Inc.