Genetic dissection of melanoma pathways in the mouse.

Abstract:

:The frequent loss of the INK4a/ARF locus, encoding for both p16(INK4a)and p19(ARF)in 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(Delta 2/3)deficiency (null for both p16(INK4a)and p19(ARF)) to promote development of melanoma, and these melanomas retain wild-type p53. Given the functional link between p19(ARF)and 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.

journal_name

Semin Cancer Biol

authors

Yang FC,Merlino G,Chin L

doi

10.1006/scbi.2000.0376

keywords:

subject

Has Abstract

pub_date

2001-06-01 00:00:00

pages

261-8

issue

3

eissn

1044-579X

issn

1096-3650

pii

S1044579X00903766

journal_volume

11

pub_type

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