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Possible associations among expression of p14 ARF , p16 INK4a , p21 WAF1/CIP1 , p27 KIP1 , and p53 accumulation and the balance of apoptosis and cell proliferation in ovarian carcinomas
Author(s) -
Saegusa Makoto,
Machida B. Daisuke,
Okayasu Isao
Publication year - 2001
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(20010901)92:5<1177::aid-cncr1436>3.0.co;2-5
Subject(s) - p14arf , immunohistochemistry , cell growth , cancer research , serous fluid , biology , apoptosis , cell cycle , pathology , western blot , tumor suppressor gene , ovarian carcinoma , carcinogenesis , ovarian cancer , medicine , cancer , gene , biochemistry , genetics
BACKGROUND Although there are several reports of changes in expression of cyclin‐dependent kinase inhibitors in ovarian carcinomas, little is known about their associations with tissue kinetics in the various histologic subtypes. METHODS In total, 131 carcinomas were immunohistochemically investigated for expression of p14 ARF (p14), p16 INK4a (p16), p21 WAF1/Cip1 (p21), and p27 Kip1 (p27). The results also were compared with data for apoptosis, cell proliferation, p53 status, and survival. Western blot and mRNA analyses were conducted on 35 malignant ovarian tumor samples. RESULTS Significant differences in tissue kinetics determined by ratios of apoptotic relative to mitotic indices were observed among histologic subtypes of ovarian carcinomas, showing a shift toward predominance of cell proliferation in serous and cell deletion in clear cell types. The expression of p16, p21, p27, and p53 was associated closely with changes in cell proliferation rather than apoptosis and survival, dependent on the subtype. Positivity for p16 and p21 in the Western blot assay was significantly related to the results for immunohistochemical but not mRNA analyses, indicating possible posttranscriptional regulation of these genes. CONCLUSIONS The findings indicate that the several cyclin‐dependent kinase inhibitors investigated are expressed differently among histologic subtypes of ovarian carcinomas, associated with differences in tissue kinetics and the balance of apoptosis and cell proliferation. Cancer 2001;92:1177–89. © 2001 American Cancer Society.