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Cheng JQ , Ruggeri B , Klein WM , Sonoda G , Altomare DA , Watson DK , Testa JR
Amplification of AKT2 in human pancreatic cancer cells and inhibition of ATK2 expression and tumorigenicity by antisense RNA
Proceedings of the National Academy of Sciences of the United States of America. 1996 Apr 16;93(8) :3636-3641
AbstractWe previously demonstrated that the putative oncogene AKT2 is amplified and overexpressed in some human ovarian carcinomas, We have now identified amplification of AKT2 in approximate to 10% of pancreatic carcinomas (2 of 18 cell lines and 1 of 10 primary tumor specimens), The two cell lines with altered AKT2 (PANC1 and ASPC1) exhibited 30-fold and 50-fold amplification of AKT2, respectively, and highly elevated levels of AKT2 RNA and protein, PANC1 cells were transfected with antisense AKT2, and several clones were established after G418 selection, The expression of AKT2 protein in these clones was greatly decreased by the antisense RNA, Furthermore, tumorigenicity in nude mice was markedly reduced in PANC1 cells expressing antisense AKT2 RNA, To examine further whether overexpression of AKT2 plays a significant role in pancreatic tumorigenesis, PANC1 cells and ASPC1 cells, as well as pancreatic carcinoma cells that do not overexpress AKT2 (COLO 357), were transfected with antisense AKT2, and their growth and invasiveness were characterized by a rat tracheal xenotransplant assay, ASPC1 and PANC1 cells expressing antisense AKT2 RNA remained confined to the tracheal lumen, whereas the respective parental cells invaded the tracheal wall, In contrast, no difference was seen in the growth pattern between parental and antisense-treated COLO 357 cells, These data suggest that overexpression of AKT2 contributes to the malignant phenotype of a subset of human ductal pancreatic cancers.
NotesTimes Cited: 169 English Article UF740 PROC NAT ACAD SCI USA