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Disruption of the RB pathway and cell‐proliferative activity in non‐small‐cell lung cancers
Author(s) -
Tanaka Hisaichi,
Fujii Yoshitaka,
Hirabayashi Hirohisa,
Miyoshi Shinichiro,
Sakaguchi Masahiro,
Yoon HyungEun,
Matsuda Hikaru
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980417)79:2<111::aid-ijc2>3.0.co;2-w
Subject(s) - cyclin d1 , retinoblastoma protein , cancer research , carcinogenesis , immunohistochemistry , retinoblastoma , biology , cell cycle , cyclin d , cyclin , cyclin b , tumor suppressor gene , cell , cancer , gene , immunology , genetics
The pathway consisting of retinoblastoma protein (pRB), cyclin D1 and p16 (RB pathway) which is involved in the phosphorylation of pRB plays an important role in G 1 /S progression. The disruption of this RB pathway has been reported in several types of human neoplasm. An immunohistochemical study of 101 non‐small‐cell lung cancers (NSCLCs) showed loss of p16 is in 47 tumors (46.5%) and loss of pRB in 42 tumors (41.6%). In 79 of 101 NSCLCs (78.2%), the expression of p16 and pRB was complementary ( p < 0.0001). Methylation of the cdkn2 gene was detected in 50% of p16‐negative tumors and in 11% of p16‐positive tumors. Aberrant expression of cyclin D1 was found in 45 tumors (44.5%). The cyclin‐D1‐positive tumors had significantly higher Ki‐67 indices than the cyclin‐D1‐negative tumors irrespective of the tumor p16 or pRB expression. Thus, 91 (90%) of 101 NSCLCs showed disturbed expression of at least 1 of the 3 components of the RB pathway. Our results suggest that the disruption of the RB pathway plays an important role in tumorigenesis in NSCLCs and that increased cyclin‐D1 expression leads to strong proliferative activity which may over‐ride the suppressive effect of p16 and pRB. Int. J. Cancer (Pred. Oncol.) 79:111–115, 1998.© 1998 Wiley‐Liss, Inc.