Amplification/overexpression of Aurora-A in human gastric carcinoma: potential role in differentiated type gastric carcinogenesis.
Aurora-A encodes a cell cycle regulated serine/threonine kinase that has essential functions for centrosome maturation and chromosome segregation. Aurora-A is amplified and overexpressed in various human carcinomas and is suggested to be a potential oncogene. To clarify the potential role of Aurora-A in human gastric carcinoma, we examined the amplification and expression in both tumor cell lines and primary carcinoma. We examined the amplification and overexpression of Aurora-A in 9 gastric carcinoma cell lines and 88 primary gastric carcinomas using Southern and Northern blot analysis, and confirmed a protein expression by immunohistochemical staining. We also investigated the relationship between Aurora-A overexpression and clinicopathological features of the tumors. Aurora-A amplification and overexpression was observed in 29% and 44.4% of cell lines and 12.5% and 41% of primary carcinomas, respectively. There was discordance between gene amplification and transcript expression, since in a previous study DNA amplification was the main mechanism for Aurora-A activation. Aurora-A overexpression exhibited significant association with increasing age and differentiated type gastric carcinoma. It was also detected in early stage gastric cancer as well as in gastric intestinal metaplasia, which is considered as a common precursor lesion for the differentiated type gastric carcinoma, and severe dysplastic cells showed stronger protein expression. We concluded that Aurora-A overexpression may well be involved in differentiated type gastric carcinogenesis. Further evaluation of the possible roles of Aurora-A and the regulation of Aurora-A expression in malignant cells will be critically important for the development of new strategies aimed at controlling the growth of malignant cells.
Kamada
Kiyoshi
K
Department of Surgery, Nara Medical University, Kashihara, Nara 634-8522, Japan. kamada@nmu-gw.naramed-u.ac.jp
Yamada
Yukishige
Y
Hirao
Tomoko
T
Fujimoto
Heisuke
H
Takahama
Yasushi
Y
Ueno
Masatoh
M
Takayama
Tomoyoshi
T
Naito
Akihiko
A
Hirao
Shuya
S
Nakajima
Yoshiyuki
Y
D000367:Age Factors; D000368:Aged; D064127:Aurora Kinases; D015152:Blotting, Northern; D015139:Blotting, Southern; D002277:Carcinoma / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011494:Protein Kinases / Q000096:biosynthesis*; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D029867:Xenopus Proteins
D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D012333:RNA, Messenger; D029867:Xenopus Proteins; D004247:DNA; D011494:Protein Kinases; C112134:AURKA protein, Xenopus; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases