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

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

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
Volume79
Issue number2
DOIs
Publication statusPublished - 1998
Externally publishedYes

Fingerprint

Non-Small Cell Lung Carcinoma
Cyclin D1
Neoplasms
Retinoblastoma Protein
Methylation
Carcinogenesis
Phosphorylation
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Disruption of the RB pathway and cell-proliferative activity in non- small-cell lung cancers. / Tanaka, Hisaichi; Fujii, Yoshitaka; Hirabayashi, Hirohisa; Miyoshi, Shinichiro; Sakaguchi, Masahiro; Yoon, Hyung Eun; Matsuda, Hikaru.

In: International Journal of Cancer, Vol. 79, No. 2, 1998, p. 111-115.

Research output: Contribution to journalArticle

Tanaka, Hisaichi ; Fujii, Yoshitaka ; Hirabayashi, Hirohisa ; Miyoshi, Shinichiro ; Sakaguchi, Masahiro ; Yoon, Hyung Eun ; Matsuda, Hikaru. / Disruption of the RB pathway and cell-proliferative activity in non- small-cell lung cancers. In: International Journal of Cancer. 1998 ; Vol. 79, No. 2. pp. 111-115.
@article{f682bd5e2a8f417e805398bfc654f7e5,
title = "Disruption of the RB pathway and cell-proliferative activity in non- small-cell lung cancers",
abstract = "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.",
author = "Hisaichi Tanaka and Yoshitaka Fujii and Hirohisa Hirabayashi and Shinichiro Miyoshi and Masahiro Sakaguchi and Yoon, {Hyung Eun} and Hikaru Matsuda",
year = "1998",
doi = "10.1002/(SICI)1097-0215(19980417)79:2<111::AID-IJC2>3.0.CO;2-W",
language = "English",
volume = "79",
pages = "111--115",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Disruption of the RB pathway and cell-proliferative activity in non- small-cell lung cancers

AU - Tanaka, Hisaichi

AU - Fujii, Yoshitaka

AU - Hirabayashi, Hirohisa

AU - Miyoshi, Shinichiro

AU - Sakaguchi, Masahiro

AU - Yoon, Hyung Eun

AU - Matsuda, Hikaru

PY - 1998

Y1 - 1998

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0031895370&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031895370&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1097-0215(19980417)79:2<111::AID-IJC2>3.0.CO;2-W

DO - 10.1002/(SICI)1097-0215(19980417)79:2<111::AID-IJC2>3.0.CO;2-W

M3 - Article

C2 - 9583722

AN - SCOPUS:0031895370

VL - 79

SP - 111

EP - 115

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 2

ER -