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

Oncogene volume 28, pages 1393–1399 (2009)Cite this article

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.

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Acknowledgements

We thank Drs Erica Jackson and Alejandro Sweet-Cordero for critical reading of the article and Dr Jeffrey Whitsett for the generous gift of SP-C antibodies. This work was supported by a Damon Runyon Cancer Research Foundation Scholar Award (JS) and by a post-doctoral fellowship from the American Lung Association (KP).

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Author notes

  1. V M Ho and B E Schaffer: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatrics and Genetics, Stanford Medical School, Stanford, CA, USA

    V M Ho, B E Schaffer, K S Park & J Sage

  2. Department of Pathology, Cancer Research Institute, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA

    A N Karnezis

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  1. V M Ho
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  2. B E Schaffer
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  3. A N Karnezis
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Correspondence to J Sage.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Ho, V., Schaffer, B., Karnezis, A. et al. The retinoblastoma gene Rb and its family member p130 suppress lung adenocarcinoma induced by oncogenic K-Ras. Oncogene 28, 1393–1399 (2009). https://doi.org/10.1038/onc.2008.491

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