AMPLIFICATION OF AKT2 IN HUMAN PANCREATIC-CANCER CELLS AND INHIBITIONOF ATK2 EXPRESSION AND TUMORIGENICITY BY ANTISENSE RNA

We previously demonstrated that the putative oncogene AKT2 is amplifie d and overexpressed in some human ovarian carcinomas, We have now iden tified amplification of AKT2 in approximate to 10% of pancreatic carci nomas (2 of 18 cell lines and 1 of 10 primary tumor specimens), The tw o cell lines with altered AKT2 (PANC1 and ASPC1) exhibited 30-fold and 50-fold amplification of AKT2, respectively, and highly elevated leve ls of AKT2 RNA and protein, PANC1 cells were transfected with antisens e AKT2, and several clones were established after G418 selection, The expression of AKT2 protein in these clones was greatly decreased by th e antisense RNA, Furthermore, tumorigenicity in nude mice was markedly reduced in PANC1 cells expressing antisense AKT2 RNA, To examine furt her whether overexpression of AKT2 plays a significant role in pancrea tic tumorigenesis, PANC1 cells and ASPC1 cells, as well as pancreatic carcinoma cells that do not overexpress AKT2 (COLO 357), were transfec ted with antisense AKT2, and their growth and invasiveness were charac terized 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 c ontrast, no difference was seen in the growth pattern between parental and antisense-treated COLO 357 cells, These data suggest that overexp ression of AKT2 contributes to the malignant phenotype of a subset of human ductal pancreatic cancers.