Human semaphorins A(V) and IV reside in the 3p21.3 small cell lung cancer deletion region and demonstrate distinct expression patterns.

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.
AuthorsY Sekido, S Bader, F Latif, J Y Chen, F M Duh, M H Wei, J P Albanesi, C C Lee, M I Lerman, J D Minna
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 93 Issue 9 Pg. 4120-5 (Apr 30 1996) ISSN: 0027-8424 [Print] UNITED STATES
PMID8633026 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • DNA Primers
  • Glycoproteins
  • Nerve Growth Factors
  • Semaphorin-3A
  • semaphorin A(V)
  • semaphorin IV
  • Amino Acid Sequence
  • Base Sequence
  • Carcinoma, Small Cell (genetics)
  • Cell Line
  • Chromosome Deletion
  • Chromosome Mapping
  • Chromosomes, Human, Pair 3
  • DNA Primers
  • Female
  • Gene Expression
  • Gene Library
  • Glycoproteins (biosynthesis, genetics)
  • Humans
  • Lung Neoplasms (genetics)
  • Male
  • Molecular Sequence Data
  • Nerve Growth Factors (biosynthesis, genetics)
  • Open Reading Frames
  • Organ Specificity
  • Phylogeny
  • Placenta (metabolism)
  • Polymerase Chain Reaction
  • Pregnancy
  • Protein Biosynthesis
  • Restriction Mapping
  • Semaphorin-3A
  • Sequence Homology, Amino Acid

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