Tumour-amplified kinase BTAK is amplified and overexpressed in gastric cancers with possible involvement in aneuploid formation.
Our recent analysis of gastric cancers using comparative genomic hybridization (CGH) revealed a novel high frequent copy number increase in the long arm of chromosome 20. Tumour-amplified kinase BTAK was recently cloned from breast cancers and mapped on 20q13 as a target gene for this amplification in human breast cancers. In the study presented here, we analysed BTAK copy-number and expression, and their relation to the ploidy pattern in 72 primary gastric cancers. Furthermore, wild-type BTAK and its deletion mutants were transfected to gastric cancers to examine changes in cell proliferation and DNA ploidy pattern. Evaluation of 72 unselected primary gastric cancers found BTAK amplification in 5% and overexpression in more than 50%. All four clinical samples with BTAK amplification showed aneuploidy and poor prognosis. Transfection of BTAK in near-diploid gastric cancers induced another aneuploid cell population. In contrast, the c-terminal-deleted mutant of BTAK induced no effect in DNA ploidy pattern and inhibited gastric cancer cell proliferation. These results suggest that BTAK may be involved in gastric cancer cell aneuploid formation, and is a candidate gene for the increase in the number of copies of the 20q, and thus may contribute to an increase in the malignant phenotype of gastric cancer.
Department of Digestive Surgery, Kyoto Prefectural University of Medicine, Japan.
C
C
Sakakura
A
A
Hagiwara
R
R
Yasuoka
Y
Y
Fujita
M
M
Nakanishi
K
K
Masuda
K
K
Shimomura
Y
Y
Nakamura
J
J
Inazawa
T
T
Abe
H
H
Yamagishi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D064096:Aurora Kinase A; D064127:Aurora Kinases; D001483:Base Sequence; D017931:DNA Primers; D006801:Humans; D015151:Immunoblotting; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
D017931:DNA Primers; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases