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Suppression of growth in vitro and tumorigenicity in vivo of human carcinoma cell lines by transfected p16 INK4
Author(s) -
Spillare Elisa A.,
Okamoto Aikou,
Hagiwara Koichi,
Demetrick Douglas J.,
Serrano Manuel,
Beach David,
Harris Curtis C.
Publication year - 1996
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/(sici)1098-2744(199605)16:1<53::aid-mc7>3.0.co;2-p
Subject(s) - biology , transfection , tumor suppressor gene , cell culture , clone (java method) , cell growth , retinoblastoma protein , in vivo , in vitro , cancer research , microbiology and biotechnology , gene , cell cycle , carcinogenesis , genetics
The function of p16 INK4 as a putative tumor suppressor gene was examined by investigating its ability to inhibit the growth of cancer cell lines in vitro and tumor formation in vivo. A p16 INK4 cDNA expression vector was transfected into five human cancer cell lines that varied in their p16 INK4 and retinoblastoma (Rb) status. Suppression of colony‐forming efficiency was seen in four cell lines. Of two cell lines wild type for p16 INK4 but null for Rb protein expression, one (Hep 3B) showed inhibition of colony formation, whereas the other (Saos‐2) did not. This observation may demonstrate involvement of p16 INK4 independent of Rb. The transfected p16 INK4 gene was frequently selected against and lost during continued growth in vitro. When compared to the colon carcinoma cell line (DLD‐1), p16 INK4 ‐transfected DLD‐1 clone 1 cells were less tumorigenic in athymic nude mice. Tumors arising from p16 INK4 ‐transfected DLD‐1 clones, which were growth suppressed in vitro, either lost the integrated exogenous p16 INK4 or expressed reduced amounts of p16 INK4 protein. Therefore, p16 INK4 was also selected against during tumor formation in vivo. These data are consistent with the hypothesis that p16 INK4 is a tumor suppressor gene. (This article is a US Government work and, as such, is in the public domain in the United States of America.) © 1996 Wiley‐Liss, Inc.