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

Yoshitaka Sekido, Scott Bader, Farida Latif, Jeou Yuan Chen, Fuh Mei Duh, Ming Hui Wei, Joseph P. Albanesi, Cheng Chi Lee, Michael I. Lerman, John D. Minna

Research output: Contribution to journalArticle

214 Scopus citations

Abstract

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 κ70 kb apart flanking two GTP-binding protein genes. GNAI-2 and GNAT-1. In contrast, other human semaphorin gene sequences (human semaphorin lit 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 nf 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.

Original languageEnglish (US)
Pages (from-to)4120-4125
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number9
DOIs
StatePublished - Apr 30 1996

Keywords

  • G protein
  • collapsin
  • growth cone guidance
  • recessive oncogene

ASJC Scopus subject areas

  • General

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