title: A candidate tumor suppressor gene, H37, from the human lung cancer tumor suppressor locus 3p21.3.
abstract: 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.
authors.affiliation: Department of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Juliana J
authors.initials: JJ
authors.lastname: Oh
authors.forename: Alison R
authors.initials: AR
authors.lastname: West
authors.forename: Michael C
authors.initials: MC
authors.lastname: Fishbein
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Slamon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism; D002455:Cell Division / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection
chemical_list: D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases