Role of the INK4a locus in tumor suppression and cell mortality

Manuel Serrano, Han Woong Lee, Lynda Chin, Carlos Cordon-Cardo, David Beach, Ronald A. DePinho

Research output: Contribution to journalArticle

1312 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)27-37
Number of pages11
JournalCell
Volume85
Issue number1
DOIs
Publication statusPublished - 1996 Apr 5

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Tumors
Gene encoding
Fibroblasts
Mortality
Overlapping Genes
Neoplasms
Cell proliferation
Pancreatic Neoplasms
Melanoma
Cell Cycle
Cells
Cell Proliferation
Phenotype
Growth
Genes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Serrano, M., Lee, H. W., Chin, L., Cordon-Cardo, C., Beach, D., & DePinho, R. A. (1996). Role of the INK4a locus in tumor suppression and cell mortality. Cell, 85(1), 27-37. https://doi.org/10.1016/S0092-8674(00)81079-X
Serrano, Manuel ; Lee, Han Woong ; Chin, Lynda ; Cordon-Cardo, Carlos ; Beach, David ; DePinho, Ronald A. / Role of the INK4a locus in tumor suppression and cell mortality. In: Cell. 1996 ; Vol. 85, No. 1. pp. 27-37.
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Serrano, M, Lee, HW, Chin, L, Cordon-Cardo, C, Beach, D & DePinho, RA 1996, 'Role of the INK4a locus in tumor suppression and cell mortality', Cell, vol. 85, no. 1, pp. 27-37. https://doi.org/10.1016/S0092-8674(00)81079-X

Role of the INK4a locus in tumor suppression and cell mortality. / Serrano, Manuel; Lee, Han Woong; Chin, Lynda; Cordon-Cardo, Carlos; Beach, David; DePinho, Ronald A.

In: Cell, Vol. 85, No. 1, 05.04.1996, p. 27-37.

Research output: Contribution to journalArticle

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Serrano M, Lee HW, Chin L, Cordon-Cardo C, Beach D, DePinho RA. Role of the INK4a locus in tumor suppression and cell mortality. Cell. 1996 Apr 5;85(1):27-37. https://doi.org/10.1016/S0092-8674(00)81079-X