Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149925 (small cell lung cancer)
 6,491 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Semaphorins and collapsins make up a family of conserved genes that encode nerve growth cone guidance signals. We have identified two additional members of the human semaphorin family [human semaphorin A(V) and human semaphorin IV] in chromosome region 3p21.3, where several small cell lung cancer (SCLC) cell lines exhibit homozygous deletions indicative of a tumor suppressor gene. Human semaphorin A(V) has 86% amino acid homology with murine semaphorin A, whereas semaphorin IV is most closely related to murine semaphorin E, with 50% homology. These semaphorin genes are approximately 70 kb apart flanking two GTP-binding protein genes, GNAI-2 and GNAT-1. In contrast, other human semaphorin gene sequences (human semaphorin III and homologues of murine semaphorins B and C) are not located on chromosome 3. Human semaphorin A(V) is translated in vitro into a 90-kDa protein, which accumulates at the endoplasmic reticulum. The human semaphorin A(V) (3.4-kb mRNA) and IV (3.9- and 2.9-kb mRNAs) genes are expressed abundantly but differentially in a variety of human neural and nonneural tissues. Human semaphorin A(V) was expressed in only 1 out of 23 SCLCs and 7 out of 16 non-SCLCs, whereas semaphorin IV was expressed in 19 out of 23 SCLCs and 13 out of 16 non-SCLCs. Mutational analysis in semaphorin A(V) revealed mutations (germ line in one case) in 3 of 40 lung cancers. Our data suggest the need to determine the function of human semaphorins A(V) and IV in nonneural tissues and their role in the pathogenesis of lung cancer.
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PMID:Human semaphorins A(V) and IV reside in the 3p21.3 small cell lung cancer deletion region and demonstrate distinct expression patterns. 863 26

Small cell lung cancer (SCLC) has been correlated with a deletion in the short arm of chromosome 3, with the region 3p21 being lost from one homolog in almost all cases. Two SCLC cell lines have homozygous deletions in 3p21, and these deletions overlap with a fragment of chromosome 3 that has tumor suppression activity in vivo. We have isolated some cDNA clones from this region that are homologous to the genes constituting the semaphorin family. They represent a novel human semaphorin, termed sema III/F (HGMW-approved symbol SEMA3F), which is expressed as a 3.8-kb transcript in a variety of cell lines and tissues; it is detected as early as Embryonic Day 10 in mouse development. There is high expression in mammary gland, kidney, fetal brain, and lung and lower expression in heart and liver. Although there is reduced expression of this gene in several SCLC lines, no mutations were found. This semaphorin homolog has characteristics of a secreted member of the semaphorin III family, with 52% identity with mouse semaphorin E and 49% identity with chicken collapsin/semaphorin D.
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PMID:Isolation of the human semaphorin III/F gene (SEMA3F) at chromosome 3p21, a region deleted in lung cancer. 878 19