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.
Sekido
Y
Y
Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Bader
S
S
Latif
F
F
Chen
J Y
JY
Duh
F M
FM
Wei
M H
MH
Albanesi
J P
JP
Lee
C C
CC
Lerman
M I
MI
Minna
J D
JD
D000595:Amino Acid Sequence; D001483:Base Sequence; D018288:Carcinoma, Small Cell / Q000235:genetics*; D002460:Cell Line; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D017931:DNA Primers; D005260:Female; D015870:Gene Expression; D015723:Gene Library; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics*; D016366:Open Reading Frames; D009928:Organ Specificity; D010802:Phylogeny; D010920:Placenta / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D014176:Protein Biosynthesis; D015183:Restriction Mapping; D040121:Semaphorin-3A; D017386:Sequence Homology, Amino Acid
D017931:DNA Primers; D006023:Glycoproteins; D009414:Nerve Growth Factors; D040121:Semaphorin-3A; C099435:semaphorin A(V); C099436:semaphorin IV