Somatic cell type specific gene transfer reveals a tumor-promoting function for p21Waf1/Cip1 Journal Article
| Authors: | Liu, Y.; Yeh, N.; Zhu, X. H.; Leversha, M.; Cordon-Cardo, C.; Ghossein, R.; Singh, B.; Holland, E.; Koff, A. |
| Article Title: | Somatic cell type specific gene transfer reveals a tumor-promoting function for p21Waf1/Cip1 |
| Abstract: | How proteins participate in tumorigenesis can be obscured by their multifunctional nature. For example, depending on the cellular context, the cdk inhibitors can affect cell proliferation, cell motility, apoptosis, receptor tyrosine kinase signaling, and transcription. Thus, to determine how a protein contributes to tumorigenesis, we need to evaluate which functions are required in the developing tumor. Here we demonstrate that the RCAS/TvA system, originally developed to introduce oncogenes into somatic cells of mice, can be adapted to allow us to define the contribution that different functional domains make to tumor development. Studying the development of growth-factor-induced oligodendroglioma, we identified a critical role for the Cy elements in p21, and we showed that cyclin D1T286A, which accumulates in the nucleus of p21-deficient cells and binds to cdk4, could bypass the requirement for p21 during tumor development. These genetic results suggest that p21 acts through the cyclin D1-cdk4 complex to support tumor growth, and establish the utility of using a somatic cell modeling system for defining the contribution proteins make to tumor development. ©2007 European Molecular Biology Organization. |
| Keywords: | controlled study; nonhuman; glioma; protein function; animal cell; mouse; animals; mice; mus; complex formation; somatic cell; embryo; cell line; animal experiment; animal model; protein binding; carcinogenesis; cell type; gene transfer; genetic vectors; mice, transgenic; receptors, virus; platelet-derived growth factor; oligodendroglioma; cell nucleus; cyclin-dependent kinase inhibitor p21; tumor growth; molecular biology; cyclin d1; cyclins; protein p21; bioaccumulation; cyclin dependent kinase 4; retroviridae; cyclin-dependent kinase 4; cyclin d; chickens; gene transfer techniques; cyclin dependent kinase inhibitor 1; cdk inhibitor; oligodendrocyte; avian proteins |
| Journal Title: | EMBO Journal |
| Volume: | 26 |
| Issue: | 22 |
| ISSN: | 0261-4189 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2007-11-14 |
| Start Page: | 4683 |
| End Page: | 4693 |
| Language: | English |
| DOI: | 10.1038/sj.emboj.7601886 |
| PUBMED: | 17948060 |
| PROVIDER: | scopus |
| PMCID: | PMC2048756 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 17" - "Export Date: 17 November 2011" - "CODEN: EMJOD" - "Source: Scopus" |
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