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Tumor‐suppressive activity of the growth arrest‐specific gene GAS1 in human tumor cell lines
Author(s) -
Evdokiou Andreas,
Cowled Prudence A.
Publication year - 1998
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(19980209)75:4<568::aid-ijc13>3.0.co;2-5
Subject(s) - transfection , biology , ht1080 , plasmid , microbiology and biotechnology , cell growth , tumor suppressor gene , cell culture , mutant , mdm2 , growth inhibition , a549 cell , cancer research , gene , carcinogenesis , genetics
The GAS1 gene product induces growth arrest through a p53‐dependent mechanism. To investigate whether GAS 1 is a tumor suppressor gene, we transfected GAS1‐negative human tumor cells with GAS 1 plasmids and analyzed growth characteristics of stable transfectants. When a constitutively expressing GAS 1 plasmid was transfected into A549 cells, no stable colonies expressing GAS1 were isolated. When A549 cells were transfected with a dexamethasone‐inducible GAS 1 plasmid, expression of GAS1 inhibited growth in vitro, and fewer slow‐growing tumors arose in nude mice. GAS1 also inhibited proliferation of an HT1080 subline with wild‐type (wt) p53 and normal MDM2. However, when the HT1080 subline HTD114 was transfected with the constitutive GAS 1 plasmid, there was no reduction in colony number. GAS1‐transfectant clones had unaltered growth in vitro, were morphologically unchanged and showed no difference in their ability to form tumors in nude mice. Although HTD114 cells contain wt p53, levels of MDM2 were elevated by 10–15 fold. The HT1080‐6TGc5 subline with mutant p53 and normal MDM2 was also refractory to GAS1. Our results show that GAS1 suppresses the growth and tumorigenicity of human tumor cells and overexpression of MDM2 or p53 mutation inhibits the GAS1‐mediated growth‐suppressing pathway. Int. J. Cancer 75:568–577, 1998. © 1998 Wiley‐Liss, Inc.