Amplification and over-expression of the AIB1 nuclear receptor co-activator gene in primary gastric cancers.
Our analysis of chromosomal aberrations in primary gastric cancers using comparative genomic hybridization has revealed novel, high and frequent copy number increases in the long arm of chromosome 20, indicating that this region contains novel amplified genes involved in gastric cancer progression. AIB1, a member of the steroid receptor co-activator-1 family, has been cloned on 20q12 as a candidate target gene for this amplification in human breast cancers. In this study, we examined the numbers of AIB1 copies as well as their expression and relation to clinico-pathological features in 72 primary gastric cancers. AIB1 amplification was observed in 7% and over-expression in 40% of the specimens. AIB1 amplification always coincided with its over-expression, but several cases showed AIB1 over-expression without amplification, suggesting that expression of AIB1 is regulated not only by gene amplification but also by other mechanisms, such as transcriptional activation, in human gastric cancer. Gastric cancers with AIB1 amplification showed extensive lymph node metastases, liver metastases and poorer prognosis compared to those without amplification. Our results suggest that amplification and over-expression of AIB1 are likely to increase the number of malignant phenotypes of gastric cancers and that it can be expected to be useful as a marker of poor prognosis.
Sakakura
C
C
Department of Gastroenterological Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Hagiwara
A
A
Yasuoka
R
R
Fujita
Y
Y
Nakanishi
M
M
Masuda
K
K
Kimura
A
A
Nakamura
Y
Y
Inazawa
J
J
Abe
T
T
Yamagishi
H
H
D000328:Adult; D015152:Blotting, Northern; D015139:Blotting, Southern; D018572:Disease-Free Survival; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D005784:Gene Amplification; D015870:Gene Expression; D051548:Histone Acetyltransferases; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D056920:Nuclear Receptor Coactivator 1; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
D014157:Transcription Factors; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1