中国生物工程杂志

［1］ Katso R, Okkenhaug K,Ahmadi K, et al. Cellular function of phosphoinositide3kinases: implications for development, homeostasis, and cancer. Annu Rev Ceff Dev Biof, 2001, 17: 615~675 ［2］ Cantley L C. The phosphoinositide 3kinase pathway. Science, 2002, 296: 1655~1657 ［3］ Kim D, Kim S, Koh H, et al. Akt/PKB promotes cancer cell invasion via increased motility and metalloproteinase production. FASEB J, 2001, 15: 1953~1962 ［4］ Grille S J, Bellacosa A, Upson J, et al. The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines. Cancer Res, 2003, 63: 2172~2178 ［5］ Arboleda M J, Lyons J F, Kabbinavar F F, et al. Overexpression of AKT2/protein kinase Bbeta leads to upregulation of beta1 integrins, increased invasion, and metastasis of human breast and ovarian cancer cells. Cancer Res, 2003, 63: 196~206 ［6］ Hutchinson J N, Jin J, Cardiff R D, et al. Activation of Akt1 (PKBalpha) can accelerate ErbB2mediated mammary tumorigenesis but suppresses tumor invasion. Cancer Res, 2004, 64: 3171~3178 ［7］ Staal S P. Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2: amplification of AKT1 in a primary human gastric adenocarcinoma. Proc Natl Acad Sci U S A, 1987, 84: 5034~5037 ［8］ Tanno S, Mitsuuchi Y, Altomare D A, et al. AKT activation upregulates insulinlike growth factor I receptor expression and promotes invasiveness of human pancreatic cancer cells. Cancer Res, 2001, 61: 589~593 ［9］ Enomoto A, Murakami H, Asai N, et al. Akt/PKB regulates actin organization and cell motility via Girdin/APE. Dev Cell, 2005, 9: 389~402 ［10］ YoeliLerner M, Yiu G K, Rabinovitz I, et al. Akt blocks breast cancer cell motility and invasion through the transcription factor NFAT. Mol Cell, 2005, 20: 539~550 ［11］ Ju X, Katiyar S, Wang C, et al. Akt1 governs breast cancer progression in vivo. Proc Natl Acad Sci U S A, 2007, 104: 7438~7443 ［12］ Liu H, Radisky D C, Nelson C M, et al. Mechanism of Akt1 inhibition of breast cancer cell invasion reveals a protumorigenic role for TSC2. Proc Natl Acad Sci U S A, 2006, 103: 4134~4139 ［13］ Rychahou P G, Kang J, Gulhati P, et al. Akt2 overexpression plays a critical role in the establishment of colorectal cancer metastasis. Proc Natl Acad Sci U S A (in press), 2008 ［14］ Cheung M, Sharma A, Madhunapantula S V, et al. Akt3 and mutant V600E BRaf cooperate to promote early melanoma development. Cancer Res, 2008, 68: 3429~3439 ［15］ Young C D, Nolte E C, Lewis A, et al. Activated Akt1 accelerates MMTVcErbB2 mammary tumourigenesis in mice without activation of ErbB3. Breast Cancer Res, 2008, 10:R70 ［16］ Li Y, Dowbenko D, Lasky L A. AKT/PKB phosphorylation of p21Cip/WAF1 enhances protein stability of p21Cip/WAF1 and promotes cell survival. J Biol Chem, 2002, 277: 11352~11361 ［17］ Albanese C, Wu K, D'Amico M, et al. IKKalpha regulates mitogenic signaling through transcriptional induction of cyclin D1 via Tcf. Mol Biol Cell, 2003, 14: 585~599 ［18］ Manning B D, Logsdon M N, Lipovsky A I, et al. Feedback inhibition of Akt signaling limits the growth of tumors lacking Tsc2. Genes Dev, 2005, 19: 1773~1778 ［19］ Yiu G K, Toker A. NFAT induces breast cancer cell invasion by promoting the induction of cyclooxygenase-2. J Biol Chem, 2006, 281: 12210~12217