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Reduced expression of cyclin‐dependent kinase inhibitor p27 Kip1 is an indicator of malignant behavior in oral squamous cell carcinoma
Author(s) -
Kudo Yasusei,
Takata Takashi,
Yasui Wataru,
Ogawa Ikuko,
Miyauchi Mutsumi,
Takekoshi Toshitsugu,
Tahara Eiichi,
Nikai Hiromasa
Publication year - 1998
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/(sici)1097-0142(19981215)83:12<2447::aid-cncr7>3.0.co;2-a
Subject(s) - immunohistochemistry , western blot , cancer research , pathology , metastasis , medicine , dysplasia , kinase , skp2 , cyclin dependent kinase , cancer , cell culture , carcinoma , biology , cell cycle , ubiquitin , gene , ubiquitin ligase , microbiology and biotechnology , biochemistry , genetics
BACKGROUND Reduced expression of the cyclin‐dependent kinase inhibitor p27 Kip1 has been reported to correlate with poor survival in cohorts of breast and colorectal carcinoma patients. Posttranslational ubiquitin‐mediated proteasomal proteolysis is related to p27 Kip1 protein levels. However, to the authors' knowledge, no previous study has examined the expression of p27 Kip1 in oral squamous cell carcinoma (OSCC). METHODS To examine the expression of p27 Kip1 and its clinicopathologic roles in OSCC, the authors studied the expression of p27 Kip1 protein by immunohistochemistry in deparaffinized tissue sections of 20 normal oral mucosa specimens, 22 epithelial dysplasia specimens, and 70 OSCCs, and analyzed its correlation with clinicopathologic parameters. They also studied the expression of p27 Kip1 mRNA and protein in six OSCC cell lines by Northern blot and Western blot analysis. To examine the mechanism of reduced expression of p27 Kip1 , OSCC cell lines were treated with the proteasome inhibitor LLnV. RESULTS All the normal oral mucosa specimens and 73% (16 of 22) of the oral epithelial dysplasia specimens expressed p27 Kip1 at high levels, whereas 87% of the OSCCs (61 of 70) showed reduced expression of p27 Kip1 . Furthermore, the levels of expression of this protein were significantly lower in carcinomas with metastasis than those without metastasis. Although OSCC cell lines expressed p27 Kip1 mRNA at various levels, most of them expressed p27 Kip1 protein at lower or undetectable levels. LLnV induced the expression of p27 Kip1 protein in HSC2 cells, in which p27 Kip1 protein was originally undetectable. CONCLUSIONS These findings suggest that 1) reduced expression of p27 Kip1 may correlate with the development and progression of OSCC and can be an indicator of malignant behavior of this neoplasm, and 2) increased proteasome‐mediated degradation may play an important role in the reduction of p27 Kip1 protein expression. Cancer 1998;83:2447‐2455. © 1998 American Cancer Society.