Biological significance of gene amplification in carcinogenesis.
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.
Terada
M
M
National Cancer Center Research Institute, Tokyo, Japan.
Sakamoto
H
H
Ohmura
Y
Y
Tsuruta
H
H
Akiyama
N
N
Sasaki
H
H
Katoh
M
M
Hattori
Y
Y
Yoshida
T
T
D004938:Esophageal Neoplasms / Q000235:genetics; D051518:Fibroblast Growth Factor 3; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000235:genetics; D005784:Gene Amplification; D015870:Gene Expression; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics; D009369:Neoplasms / Q000209:etiology / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011519:Proto-Oncogenes; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor; D013274:Stomach Neoplasms / Q000235:genetics
C496444:FGF3 protein, human; C496445:FGF4 protein, human; D051518:Fibroblast Growth Factor 3; D051519:Fibroblast Growth Factor 4; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors; C496353:FGFR2 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2