Functional evidence for a second tumor suppressor gene on human chromosome 17.
The development and progression of human tumors often involves inactivation of tumor suppressor gene function. Observations that specific chromosome deletions correlate with distinct groups of cancer suggest that some types of tumors may share common defective tumor suppressor genes. In support of this notion, our initial studies showed that four human carcinoma cell lines belong to the same complementation group for tumorigenic potential. In this investigation, we have extended these studies to six human soft tissue sarcoma cell lines. Our data showed that hybrid cells between a peripheral neuroepithelioma (PNET) cell line and normal human fibroblasts or HeLa cells were nontumorigenic. However, hybrid cells between the PNET cell line and five other soft tissue sarcoma cell lines remained highly tumorigenic, suggesting at least one common genetic defect in the control of tumorigenic potential in these cells. To determine the location of this common tumor suppressor gene, we examined biochemical and molecular polymorphic markers in matched pairs of tumorigenic and nontumorigenic hybrid cells between the PNET cell line and a normal human fibroblast. The data showed that loss of the fibroblast-derived chromosome 17 correlated with the conversion from nontumorigenic to tumorigenic cells. Transfer of two different chromosome 17s containing a mutant form of the p53 gene into the PNET cell line caused suppression of tumorigenic potential, implying the presence of a second tumor suppressor gene on chromosome 17.
Chen
P
P
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill 27599.
Ellmore
N
N
Weissman
B E
BE
D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D004273:DNA, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016161:Genes, Retinoblastoma; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006367:HeLa Cells; D006801:Humans; D006822:Hybrid Cells; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D011110:Polymorphism, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D012509:Sarcoma / Q000235:genetics; D012983:Soft Tissue Neoplasms / Q000235:genetics; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D009838:Oligodeoxyribonucleotides