Biological significance of gene amplification in carcinogenesis

Princess Takamatsu Symp. 1991:22:371-80.

Abstract

K-SAM gene was originally isolated as an amplified gene in a stomach cancer cell line by in-gel DNA renaturation method. K-SAM encodes a membrane receptor with tyrosine kinase and is often amplified in poorly differentiated type of stomach cancer, while c-ERBB-2 is often amplified in well differentiated type of stomach cancer. There are several forms of K-SAM mRNAs which are generated by alternative splicing, and two types of K-SAM protein without transmembrane region. The ligand of K-SAM is considered to be growth factor(s) belonging to fibroblast growth factor (FGF) or heparin binding growth factor (HBFG) family. We have also frequently found amplification of HST-1 or HSTF1 gene in esophageal cancer. HST-1 gene, originally found as a transforming gene, is located on human chromosome 11q13, and it locates 35 kbp apart from its related gene, INT-2. Neither of the genes was expressed even in cancer cells with the co-amplification. By cosmid walking, we have identified at least two genes, designated tentatively as EXP1 and EXP2, on the same amplicon as HST-1 and INT-2, and the mRNAs for EXP1 and EXP2 genes were increased in amounts proportional to the degree of amplification.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Esophageal Neoplasms / genetics
  • Fibroblast Growth Factor 3
  • Fibroblast Growth Factor 4
  • Fibroblast Growth Factors / genetics
  • Gene Amplification*
  • Gene Expression
  • Humans
  • Neoplasm Proteins / genetics
  • Neoplasms / etiology
  • Neoplasms / genetics*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogenes*
  • Receptor Protein-Tyrosine Kinases*
  • Receptor, Fibroblast Growth Factor, Type 2
  • Receptors, Fibroblast Growth Factor*
  • Stomach Neoplasms / genetics

Substances

  • FGF3 protein, human
  • FGF4 protein, human
  • Fibroblast Growth Factor 3
  • Fibroblast Growth Factor 4
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • Receptors, Fibroblast Growth Factor
  • Fibroblast Growth Factors
  • FGFR2 protein, human
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 2