Expression of cell cycle regulatory proteins (p53, pRb) in the human female genital tract.
OBJECTIVE
Recent studies have shown that proliferation and differentiation of various cell types is regulated by cell-cycle-related proteins, such as protein p53 and retinoblastoma protein pRb.


METHODS
Three monoclonal antibodies to p53 (PAb240, PAb421, and PAb1801) and 3H9 monoclonal antibody to pRb were utilized for localization of proteins by peroxidase immunohistochemistry in frozen tissue sections.


RESULTS
Nuclear and nucleolar p53 expression was detected in nondividing and relatively stable cells, e.g., oocytes in primordial follicles and granulosa lutein cells. On the other hand, strong cytoplasmic p53 expression was detected in proliferating and low differentiated epithelial cells of the ovarian surface epithelium, amnion, endocervix and ectocervix, indicating enhanced p53 synthesis. Not all three p53 antibodies reacted with each tissue, perhaps due to structural and conformational changes in the p53 molecule, accompanying p53 association with other proteins, e.g., tissue specific transcription factor interactions. pRb expression was usually restricted to the cell nuclei and nucleoli. However, glandular cells of the female reproductive tract showed cytoplasmic pRb expression in juxtaluminal (secretory) segments of cells, a feature not previously described in any cell type. p53 and pRb immunoreactivities declined with advanced differentiation of cells. No p53 or pRb was detected in placental syncytiotrophoblast or terminally differentiated squamous epithelial cells.


CONCLUSIONS
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 expression is confined to the cell nuclei and nucleoli. A unique cytoplasmic expression of pRb in juxtaluminal segments of glandular cells suggests a role for pRb in human female fertility and conception.
Bukovsky
A
A
Department of Obstetrics and Gynecology, University of Tennessee Medical Center at Knoxville 37920, USA.
Caudle
M R
MR
Keenan
J A
JA
Wimalasena
J
J
Foster
J S
JS
Upadhyaya
N B
NB
van Meter
S E
SE
D000911:Antibodies, Monoclonal / Q000276:immunology; D002454:Cell Differentiation; D002455:Cell Division; D002466:Cell Nucleolus / Q000378:metabolism; D002584:Cervix Uteri / Q000166:cytology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004717:Endometrium / Q000166:cytology / Q000378:metabolism; D005321:Extraembryonic Membranes / Q000378:metabolism; D005187:Fallopian Tubes / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009865:Oocytes / Q000378:metabolism; D010053:Ovary / Q000166:cytology / Q000378:metabolism*; D010920:Placenta / Q000166:cytology / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000032:analysis / Q000096:biosynthesis*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis*; D014599:Uterus / Q000166:cytology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53