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Growth arrest and suppression of tumorigenicity of bladder carcinoma cell lines induced by the P16/CDKN2 ( p16 INK4A , MTS 1 ) gene and other loci on human chromosome 9
Author(s) -
Wu Qiang,
Possati Laura,
Montesi Marco,
Gualandi Francesca,
Rimessi Paola,
Morelli Cristina,
Trabanelli Cecilia,
Barbanti Brodano Giuseppe
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960315)65:6<840::aid-ijc22>3.0.co;2-6
Subject(s) - biology , clone (java method) , transfection , tumor suppressor gene , gene , microbiology and biotechnology , chromosome , cancer research , genetics , carcinogenesis
Wild‐type P16/CDKN2 ( p16 INK4A , MTSI ) cDNA, directed by the cytomegalovirus (CMV) immediate early promoter, was transfected into RT4 and RT112 bladder‐carcinoma cell lines bearing a mutated endogenous P16/CDKN2 gene and lacking endogenous P16/CDKN2 respectively. In both cases, only transfected clones with rearranged exogenous P16/CDKN2 cDNA could be grown and propagated in cell culture. This result is reminiscent of transfection of wild‐type p53 into cells with a deleted or mutated endogenous gene and suggests that P16/CDKN2 , over‐expressed under control of the strong CMV promoter, induces growth arrest in RT4 and RT112 cells. Transfer of human chromosome 9 to RT4 cells produced RT4/H9 hybrid clones retaining the P16/CDKN2 gene, since in RT4/H9 cell clones P16/CDKN2 ‐gene expression is modulated by the physiological control of chromosomal regulatory sequences. All the RT4/H9 clones lost the entire chromosome 9, except clone 4 and clone 5, which maintained a deleted and an intact chromosome 9 respectively. Loss of several loci in 9p21, including P16/CDKN2 , in tumors induced in nude mice by clone 4 and clone 5 suggests that P16/CDKN2 or other genes in 9p21 suppress tumorigenicity in bladder‐carcinoma cells. Tumors induced by clone 4 and clone 5 show loss of markers in 9q. The regions 9q22.3, 9q32–33 and 9q34.2, which were maintained in the 2 clones and lost in their derived tumors, may contain tumor‐suppressor genes relevant in bladder carcinoma. The results of this study suggest that the P16/CDKN2 gene controls growth of bladder‐carcinoma cells when it is over‐expressed, and may be involved in the development of bladder carcinoma, but other genes in 9p21 and 9q may participate in bladder‐cancer progression. © 1996 Wiley‐Liss, Inc.