Details

Autor(en) / Beteiligte

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

Titel

Human Semaphorins A(V) and IV Reside in the 3p21.3 Small Cell Lung Cancer Deletion Region and Demonstrate Distinct Expression Patterns

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 1996-04, Vol.93 (9), p.4120-4125

Ort / Verlag

United States: National Academy of Sciences of the United States of America

Erscheinungsjahr

1996

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 ≈ 70 kb apart flanking two GTP-binding proteins 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.