Suppression of tumorigenicity of rat liver epithelial tumor cell lines by a putative human 11p11.2-p12 liver tumor suppressor locus

We have previously identified and mapped a locus within human chromosome 11 p11.2-p12 that suppresses the tumorigenic potential of a rat liver tumor ce ll line (termed GN6TF) which contains well defined chromosomal aberrations involving rat chromosomes 1, 4, 7, and 10. In the present study, we investi gated the potential of this human 11p11.2-p12 liver tumor suppressor locus to suppress the tumorigenic potential of two other rat liver tumor cell lin es (GN3TG and GP10TA) following microcell-mediated introduction of human ch romosome 11. These tumor cell lines are aneuploid and contain chromosomal a bnormalities that are similar to the GN6TF tumor line. The tumorigenic pote ntial and other phenotypic characteristics of GN3TG-11(neo) and GP10TA-11(n eo) microcell hybrid (MCH) cell lines were variable, and dependent upon the status of the introduced human chromosome 11. MCH cell lines that retained the region of 11p11.2-p12 delineated by microsatellite markers D11S1385 an d D11S903 exhibited suppression of tumorigenicity in vivo (decrease in tumo rigenicity and/or elongation of latency), whereas, the tumorigenic potentia l of one MCH line that lacked markers in this region of human 11p11.2-p12, but retained flanking markers, was not changed from that of the parental tu mor cell line. The chromosomal interval between microsatellite markers D11S 1385 and D11S903 encompasses the previously localized minimal liver tumor s uppressor region, suggesting that a common locus is responsible for tumor s uppression among the rat liver tumor cell lines examined. The results of th e present study have verified the presence of a liver tumor suppressor locu s within human 11p11.2-p12, and have identified a substantial number of mic rosatellite markers that are closely linked to this tumor suppressor region . These chromosomal markers will facilitate positional cloning of candidate genes from this region, and may prove useful for determining the involveme nt of this locus in the pathogenesis of human liver cancer.