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

Oncogene. 2009 Mar 12;28(10):1393-9. doi: 10.1038/onc.2008.491. Epub 2009 Jan 19.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenocarcinoma / prevention & control*
  • Animals
  • Genes, Retinoblastoma / physiology*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lung Neoplasms / prevention & control*
  • Mice
  • Mutation
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Retinoblastoma-Like Protein p130 / genetics
  • Retinoblastoma-Like Protein p130 / physiology*


  • Rbl2 protein, mouse
  • Retinoblastoma-Like Protein p130
  • Hras protein, mouse
  • Proto-Oncogene Proteins p21(ras)