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

We describe the isolation, growth-suppressing activity, and chromosoma l localization of the human homologue of the murine growth-arrest-spec ific gene gas1. Overexpression of h-gas1 is able to block cell prolife ration in the A549 lung carcinoma and the T24 bladder carcinoma cell l ines. No effect was observed when h-gas1 was introduced into the osteo sarcoma cell line SAOS-2 and into the adenovirus-type-5 transformed ce ll line 293. This finding is related to our previous evidence that sim ian virus 40-transformed NIH 3T3 cells are also refractory to murine g as1 overexpression, suggesting that the retinoblastoma and/or p53 gene products have an active role in mediating the growth-suppressing effe ct 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 rais e the possibility that h-gas1 may be a target for genetic alterations leading to its inactivation in tumor cells.