The retinoblastoma gene Rb and its family member p130 suppress lung adenocarcinoma induced by oncogenic K-Ras

V. M. Ho, B. E. Schaffer, Anthony Karnezis, K. S. Park, J. Sage

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Mutations of the retinoblastoma tumor suppressor gene RB are frequently observed in human cancers, but rarely in non-small cell lung carcinomas (NSCLCs). Emerging evidence also suggests that the RB-related gene p130 is inactivated in a subset of human NSCLCs. To directly test the specific tumor suppressor roles of RB and p130 in NSCLC, we crossed Rb and p130 conditional mutant mice to mice carrying a conditional oncogenic K-Ras allele. In this model, controlled oncogenic K-Ras activation leads to the development of adenocarcinoma, a major subtype of NSCLC. We found that loss of p130 accelerated the death of mice, providing direct evidence in vivo that p130 is a tumor suppressor gene, albeit a weak one in this context. Loss of Rb increased the efficiency of lung cancer initiation and resulted in the development of high-grade adenocarcinomas and rapid death. Thus, despite the low frequency of RB mutations in human NSCLCs and reports that K-Ras activation and loss of RB function are rarely found in the same human tumors, loss of Rb clearly cooperates with activation of oncogenic K-Ras in lung adenocarcinoma development in mice.

Original languageEnglish (US)
Pages (from-to)1393-1399
Number of pages7
JournalOncogene
Volume28
Issue number10
DOIs
StatePublished - Mar 12 2009
Externally publishedYes

Fingerprint

Retinoblastoma Genes
Non-Small Cell Lung Carcinoma
Tumor Suppressor Genes
Adenocarcinoma
Neoplasms
Retinoblastoma
Mutation Rate
Lung Neoplasms
Alleles
Adenocarcinoma of lung
Mutation
Genes

Keywords

  • K-Ras
  • Lung adenocarcinoma
  • Mouse model
  • p107
  • p130
  • Rb

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

The retinoblastoma gene Rb and its family member p130 suppress lung adenocarcinoma induced by oncogenic K-Ras. / Ho, V. M.; Schaffer, B. E.; Karnezis, Anthony; Park, K. S.; Sage, J.

In: Oncogene, Vol. 28, No. 10, 12.03.2009, p. 1393-1399.

Research output: Contribution to journalArticle

Ho, V. M. ; Schaffer, B. E. ; Karnezis, Anthony ; Park, K. S. ; Sage, J. / The retinoblastoma gene Rb and its family member p130 suppress lung adenocarcinoma induced by oncogenic K-Ras. In: Oncogene. 2009 ; Vol. 28, No. 10. pp. 1393-1399.
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