Changes in endometrial PTEN expression throughout the human menstrual cycle

• Published in: The journal of clinical endocrinology and metabolism Vol. 85; no. 6; pp. 2334 - 2338
• Main Authors: MUTTER, G. L, LIN, M.-C, FITZGERALD, J. T, KUM, J. B, ENG, C
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.06.2000
• Subjects: Biological and medical sciences; Endometrium - metabolism; Endometrium - pathology; Epithelial Cells - metabolism; Epithelial Cells - pathology; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Genes, Tumor Suppressor; Hormone metabolism and regulation; Humans; Immunohistochemistry; Mammalian female genital system; Menstrual Cycle - metabolism; Phosphoric Monoester Hydrolases - analysis; Phosphoric Monoester Hydrolases - genetics; PTEN Phosphohydrolase; Reverse Transcriptase Polymerase Chain Reaction; Stromal Cells - metabolism; Stromal Cells - pathology; Tumor Suppressor Proteins; Uterine Diseases - genetics; Uterine Diseases - surgery; Vertebrates: reproduction; Human; Immunohistochemistry; Pathology; Menstrual cycle; Adult; Female; Physiology; Gene expression; Endometrium; Tumor suppressor gene
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.85.6.2334

Frequent mutation of the PTEN tumor suppressor gene in endometrial adenocarcinoma has led to the prediction that its product, a phosphatase that regulates the cell cycle, apoptosis, and possibly cell adhesion, is functionally active within normal endometrial tissues. We examined PTEN expression in normal human endometrium during response to changing physiological levels of steroid hormones. PTEN ribonucleic acid levels, assessed by RT-PCR, increase severalfold in secretory compared to proliferative endometrium. This suggested that progesterone, a known antineoplastic factor for endometrial adenocarcinoma, increases PTEN levels. Immunohistochemistry with an anti-PTEN monoclonal antibody displayed a complex pattern of coordinate stromal and epithelial expression. Early in the menstrual cycle under the dominant influence of estrogens, the proliferative endometrium shows ubiquitous cytoplasmic and nuclear PTEN expression. After 3-4 days of progesterone exposure, glandular epithelium of early secretory endometrium maintains cytoplasmic PTEN protein in an apical distribution offset by expanding PTEN-free basal secretory vacuoles. By the midsecretory phase, epithelial PTEN is exhausted, but increases dramatically in the cytoplasm of stromal cells undergoing decidual change. We conclude that stromal and epithelial compartments contribute to the hormone-driven changes in endometrial PTEN expression and infer that abnormal hormonal conditions may, in turn, disrupt normal patterns of PTEN expression in this tissue.