Genetic dissection of melanoma pathways in the mouse

Authors: Clarissa Yang F.¹; Merlino G.²; Chin L.^{1, 3}

Source: Seminars in Cancer Biology, Volume 11, Number 3, June 2001 , pp. 261-268(8)

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Abstract:

The frequent loss of the INK4a/ARF locus, encoding for both p16^INK4aand p19^ARFin human melanoma, raises the question as to which INK4a/ARF gene product functions to suppress melanoma-genesis in vivo. Studies in the mouse have shown that activated RAS mutation can cooperate with INK4a^2/3deficiency (null for both p16^INK4aand p19^ARF)to promote development of melanoma, and these melanomas retain wild-type p53. Given the functional link between p19^ARFand p53, we have now shown that activated RAS can also cooperate with p53 deficiency to produce melanoma in the mouse. Moreover, genome-wide analysis of RAS-induced p53 mutant melanomas reveals alterations of key components governing RB-regulated G1/S transition, such as c-Myc. These experimental findings suggest that both RB and p53 pathways function to suppress melanocyte transformation in vivo in the mouse. Copyright 2001 Academic Press

Language: English

Document Type: Research article

Affiliations: 1: Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Mayer 448, Boston, MA 02115, USA 2: Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Building 37, Rm 2E24, Bethesda, MD 20892-4255, USA 3: Department of Dermatology, Harvard Medical School, 44 Binney Street, Boston MA 02115, Mayer 448, USA

Publication date: 2001-06-01