Amplification of AKT2 in human pancreatic cancer cells and inhibition of ATK2 expression and tumorigenicity by antisense RNA
Amplification of AKT2 in human pancreatic cancer cells and inhibition of ATK2 expression and tumorigenicity by antisense RNA
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DOI：
10.1073/pnas.93.8.3636
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发表时间：
1996-04-16
影响因子：
11.1
通讯作者：
Testa, JR
中科院分区：
文献类型：
--
作者：
Cheng, JQ;Ruggeri, B;Testa, JR
我们以前证实，假定的癌基因AKT2在一些人卵巢癌中扩增和过表达，我们现在已经确定在大约10%的胰腺癌中AKT2扩增（18个细胞系中的2个和10个原发性肿瘤标本中的1个）。（PANC 1和ASPC 1）分别表现出AKT2的30倍和50倍扩增，并且AKT2 RNA和蛋白水平高度升高，用反义AKT2转染PANC 1细胞，并且在G418筛选后建立了几个克隆，转染反义AKT2 RNA的PANC 1细胞在裸鼠体内的致瘤性明显降低。为了进一步研究AKT2的过表达是否在胰腺肿瘤的发生、PANC 1细胞和ASPC 1细胞中起重要作用，以及不过度表达AKT2的胰腺癌细胞（科洛357），用反义AKT2转染，并且通过大鼠气管异种移植测定来表征它们的生长和侵袭性，表达反义AKT2 RNA的ASPC 1和PANC 1细胞保持局限于气管腔，相反，在亲本和反义处理的科洛357细胞之间的生长模式中没有观察到差异。这些数据表明AKT2的过表达促成了人导管胰腺癌的一个子集的恶性表型。
We 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.