Disruption of the RB pathway and cell-proliferative activity in non- small-cell lung cancers

Hisaichi Tanaka, Yoshitaka Fujii, Hirohisa Hirabayashi, Shinichiro Miyoshi, Masahiro Sakaguchi, Hyung Eun Yoon, Hikaru Matsuda

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48 Citations (Scopus)


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 G1/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.

Original languageEnglish
Pages (from-to)111-115
Number of pages5
JournalInternational Journal of Cancer
Issue number2
Publication statusPublished - 1998
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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