TY - JOUR
T1 - Role of the INK4a locus in tumor suppression and cell mortality
AU - Serrano, Manuel
AU - Lee, Han Woong
AU - Chin, Lynda
AU - Cordon-Cardo, Carlos
AU - Beach, David
AU - DePinho, Ronald A.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1996/4/5
Y1 - 1996/4/5
N2 - The cell cycle inhibitor p16(INK4a) is inactivated in many human tumors and in families with hereditary melanoma and pancreatic cancer. Tumor- associated alterations in the INK4a locus may also affect the overlapping gene encoding p19(ARF) and the adjacent gene encoding p15(INK4b), both negative regulators of cell proliferation. We report the phenotype of mice carrying a targeted deletion of the INK4a locus that eliminates both p16(INK4a) and p19(ARF). The mice are viable but develop spontaneous tumors at an early age and are highly sensitive to carcinogenic treatments. INK4a- deficient primary fibroblasts proliferate rapidly and have a high colony- formation efficiency. In contrast with normal cells, the introduction of activated Ha-ras into INK4a-deficient fibroblasts can result in neoplastic transformation. These findings directly demonstrate that the INK4a locus functions to suppress neoplastic growth.
AB - The cell cycle inhibitor p16(INK4a) is inactivated in many human tumors and in families with hereditary melanoma and pancreatic cancer. Tumor- associated alterations in the INK4a locus may also affect the overlapping gene encoding p19(ARF) and the adjacent gene encoding p15(INK4b), both negative regulators of cell proliferation. We report the phenotype of mice carrying a targeted deletion of the INK4a locus that eliminates both p16(INK4a) and p19(ARF). The mice are viable but develop spontaneous tumors at an early age and are highly sensitive to carcinogenic treatments. INK4a- deficient primary fibroblasts proliferate rapidly and have a high colony- formation efficiency. In contrast with normal cells, the introduction of activated Ha-ras into INK4a-deficient fibroblasts can result in neoplastic transformation. These findings directly demonstrate that the INK4a locus functions to suppress neoplastic growth.
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U2 - 10.1016/S0092-8674(00)81079-X
DO - 10.1016/S0092-8674(00)81079-X
M3 - Article
C2 - 8620534
AN - SCOPUS:0029993450
VL - 85
SP - 27
EP - 37
JO - Cell
JF - Cell
SN - 0092-8674
IS - 1
ER -