Changes in endometrial PTEN expression throughout the human menstrual cycle

Frequent mutation of the PTEN tumor suppressor gene in endometrial adenocar cinoma has led to the prediction that its product, a phosphatase that regul ates the cell cycle, apoptosis, and possibly cell adhesion, is functionally active within normal endometrial tissues. We examined PTEN expression in n ormal human endometrium during response to changing physiological levels of steroid hormones. PTEN ribonucleic acid levels, assessed by RT-PCR, increa se severalfold in secretory compared to proliferative endometrium. This sug gested that progesterone, a known antineoplastic factor for endometrial ade nocarcinoma, increases PTEN levels. Immunohistochemistry with an anti-PTEN monoclonal antibody displayed a complex pattern of coordinate stromal and e pithelial expression. Early in the menstrual cycle under the dominant influ ence of estrogens, the proliferative endometrium dhows ubiquitous cytoplasm ic and nuclear PTEN expression. After 3-4 days of progesterone exposure, gl andular epithelium of early secretory endometrium maintains cytoplasmic PTE N protein in an apical distribution offset by expanding PTEN-free basal sec retory vacuoles. By the midsecretory phase, epithelial PTEN is exhausted, b ut increases dramatically in the cytoplasm of stromal cells undergoing deci dual change. We conclude that stromal and epithelial compartments contribut e to the hormone-driven changes in endometrial PTEN expression and infer th at abnormal hormonal conditions may, in turn, disrupt normal patterns of PT EN expression in this tissue.