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A candidate tumor suppressor gene, H37, from the human lung cancer tumor suppressor locus 3p21.3



A candidate tumor suppressor gene, H37, from the human lung cancer tumor suppressor locus 3p21.3



Cancer Research 62(11): 3207-3213



Frequent allelic loss and homozygous deletions within chromosome 3p in human lung cancers have suggested that the 3p21.3 (370-kb) region contains a critical tumor suppressor gene(s) (TSG). With the exact identity/characteristics of such a gene(s) still unconfirmed, a lack of inactivating structural mutations in the expressed genes contained within this region may indicate that the 3p TSG(s) do not fit into the classical "two-mutation" model. This report characterizes a candidate 3p TSG, H37, located within the 370-kb region. Reduced expression of the H37 transcript was found in 9 of 11 (82%) of primary non-small cell lung cancers (NSCLCs) when compared with adjacent normal tissues. Generation of an H37 antibody followed by immunohistochemical analysis of primary NSCLC specimens demonstrated that 46 of 62 (73%) of these cancers contain reduced levels of H37 protein when compared with adjacent normal bronchial cells. Moreover, introduction of the H37 cDNA into human breast cancer cells deleted of 3p21-22 reduced both anchorage-dependent and -independent cell growth in vitro. Subsequent transfection of H37 cDNA into one of the human lung cancer cell lines homozygously deleted in this region resulted in a very low yield of H37-expressing clones. H37 also suppressed anchorage-dependent and -independent growth of A9 mouse fibrosarcoma cells and inhibited tumor formation in nude mice. These data indicate a potential role for H37 as one of the 3p TSGs in human lung cancer.

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Accession: 010048465

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PMID: 12036935



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