EXPRESSION OF CELL-CYCLE REGULATORY PROTEINS (P53, PRB) IN THE HUMAN FEMALE GENITAL-TRACT

Purpose: Recent studies have shown that proliferation and differentiat ion of various cell types is regulated by cell-cycle-related proteins, such as protein p53 and retinoblastoma protein pRb. Methods: Three mo noclonal antibodies to p53 (PAb240, PAb421, and PAb1801) and 3H9 monoc lonal antibody to pRb were utilized for localization of proteins by pe roxidase immunohistochemistry in frozen tissue sections. Results: Nucl ear and nucleolar p53 expression was detected in nondividing and relat ively stable cells, e.g., oocytes in primordial follicles and granulos a lutein cells. On the other hand, strong cytoplasmic p53 expression w as detected in proliferating and low differentiated epithelial cells o f the ovarian surface epithelium, amnion, endocervix and ectocervix, i ndicating enhanced p53 synthesis. Not all three p53 antibodies reacted with each tissue, perhaps due to structural and conformational change s in the p53 molecule, accompanying p53 association with other protein s, e.g., tissue specific transcription factor interactions. pRb expres sion was usually restricted to the cell nuclei and nucleoli. However, glandular cells of the female reproductive tract showed cytoplasmic pR b expression in juxtaluminal (secretory) segments of cells, a feature not previously described in any cell type. p53 and pRb immunoreactivit ies declined with advanced differentiation of cells. No p53 or pRb was detected in placental syncytiotrophoblast or terminally differentiate d squamous epithelial cells. Conclusion: Our data indicate that large quantities of p53 are synthesized in cells leaving the cell cycle and entering differentiation. Except in glandular cells, the pRb expressio n is confined to the cell nuclei and nucleoli. A unique cytoplasmic ex pression of pRb in juxtaluminal segments of glandular cells suggests a role for pRb in human female fertility and conception.