STRUCTURE, FUNCTION, AND CHROMOSOME MAPPING OF THE GROWTH-SUPPRESSING HUMAN HOMOLOG OF THE MURINE GAS1 GENE

We describe the isolation, growth-suppressing activity, and chromosomal localization of the human homologue of the murine growth-arrest-specific gene gas1. Overexpression of h-gas1 is able to block cell proliferation in the A549 lung carcinoma and the T24 bladder carcinoma cell lines. No effect was observed when h-gas1 was introduced into the osteosarcoma cell line SAOS-2 and into the adenovirus-type-5 transformed cell line 293. This finding is related to our previous evidence that simian virus 40-transformed NIH 3T3 cells are also refractory to murine gas1 overexpression, suggesting that the retinoblastoma and/or p53 gene products have an active role in mediating the growth-suppressing effect of gas1. We also show that h-gas1 is on chromosome 9q21.3-22.1, in a region considered to be a fragile site. Altogether, the results raise the possibility that h-gas1 may be a target for genetic alterations leading to its inactivation in tumor cells.