Cyclic AMP inhibition of proliferation of hepatocellular carcinoma cells is mediated by Akt

doi:10.4161/cbt.4.11.2099

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	Cyclic AMP inhibition of proliferation of hepatocellular carcinoma cells is mediated by Akt
	Liu, LH; Xie, YL; Lou, LG
刊名	CANCER BIOLOGY & THERAPY
	2005-11
卷号	4 期号:11 页码:1240-1247
ISSN号	1538-4047
DOI	10.4161/cbt.4.11.2099
文献子类	Article
英文摘要	Cyclic AMP ( cAMP), one of the most important intracellular second messengers, has been reported to inhibit proliferation of human hepatocellular carcinoma ( HCC) cells via negatively regulating p42/44 mitogen-activated protein kinase. Here, we reported that cAMP inhibited the proliferation of HCC BEL-7402 cells via a novel mechanism. Forskolin, an activator of adenylate cyclase, inhibited fetal bovine serum ( FBS)-stimulated BEL-7402 cell proliferation in a dose- and time-dependent manner, along with the inhibition of FBS-stimulated serine/threoine protein kinase Akt ( also known as PKB) phosphorylation which is required for Akt activation and this effect was mimicked by 8-Br cAMP. Forskolin also inhibited Akt phosphorylation stimulated by other growth factors such as IGF-1, epidermal growth factor, and insulin. These inhibitions were found not only in BEL-7402 cells, but also in another HCC cell line SMMC-7721 cells. Myr-Akt ( myristolated-Akt), a constitutively active Akt which was relatively resistant to cAMP inhibition, conferred BEL-7402 cells resistance to cAMP treatment. However, overexpression of Myr-Akt alone was not sufficient to stimulate BEL-7402 cell proliferation. cAMP inhibited FBS-stimulated Akt phosphorylation in a cAMP-dependent protein kinase-dependent manner. Further studies demonstrated that cAMP inhibited FBS-induced membrane localization of 3-phosphoinositide-dependent kinase 1 ( PDK-1) which is a required process for PDK-1 to phosphorylate Akt, but had no significant effect on phosphoinositide 3-kinase activity. These results indicate that cAMP inhibition of proliferation of HCC cells is mediated by Akt and cAMP inhibits Akt activation via blocking membrane localization of PDK-1.
WOS关键词	PROTEIN-KINASE-A ; PHOSPHATIDYLINOSITOL 3-KINASE/AKT ; GROWTH-FACTOR ; REGULATES EXPRESSION ; PHOSPHORYLATED RAP1B ; RAT HEPATOCYTES ; MAP KINASE ; ACTIVATION ; P27(KIP1) ; APOPTOSIS
WOS研究方向	Oncology
语种	英语
出版者	LANDES BIOSCIENCE
WOS记录号	WOS:000236044100020
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273778]
专题	药理学第一研究室
通讯作者	Lou, LG
作者单位	Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Liu, LH,Xie, YL,Lou, LG. Cyclic AMP inhibition of proliferation of hepatocellular carcinoma cells is mediated by Akt[J]. CANCER BIOLOGY & THERAPY,2005,4(11):1240-1247.
APA	Liu, LH,Xie, YL,&Lou, LG.(2005).Cyclic AMP inhibition of proliferation of hepatocellular carcinoma cells is mediated by Akt.CANCER BIOLOGY & THERAPY,4(11),1240-1247.
MLA	Liu, LH,et al."Cyclic AMP inhibition of proliferation of hepatocellular carcinoma cells is mediated by Akt".CANCER BIOLOGY & THERAPY 4.11(2005):1240-1247.