Please wait a minute...

中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志  2009, Vol. 29 Issue (03): 14-19    
研究报告     
Akt1基因沉默降低小鼠乳腺癌细胞的肺转移能力
刘海艳,顾玉超,宓文义,于文功
中国海洋大学医药学院
Akt1 Silencing Inhibits Lung Metastasis of Murine Breast Cancer Cells
 全文: PDF(579 KB)   HTML
摘要:

Akt1是一种丝氨酸/苏氨酸蛋白激酶,参与调节细胞的代谢、生长和发育。作为一种原癌基因,Akt1在许多人类肿瘤中表达显著增高,促进肿瘤转移;但也有研究表明,Akt1的活化可抑制乳腺癌细胞的侵袭和转移。为了深入探讨Akt1在肿瘤发生发展过程中的作用,采用RNA干扰技术沉默了高转移小鼠乳腺癌细胞4T1中Akt1的表达。MTT法检测发现,Akt1沉默不影响4T1细胞的增殖能力;Transwell法检测证明,Akt1沉默可降低4T1细胞的迁移能力。与以上结果相一致,Akt1沉默不影响乳腺癌形成原位瘤的能力,但显著降低其体内肺转移能力。结果表明,Akt1在小鼠乳腺癌细胞转移过程中发挥重要作用,并提示Akt1可能成为乳腺癌治疗的靶点。

关键词: Akt1;乳腺癌;细胞迁移;肿瘤转移    
Abstract:

Akt1 is a serine-threonine protein kinase that has been implicated in the control of cellular metabolism, survival and growth. Elevated expression of Akt1 has been noted in a significant percentage of human tumors, promoting cellular metastasis. Conversely, some studies have revealed hyperactivated Akt1 inhibited the invasiveness and metastasis of breast cancer cells. To clarify the definite effect of Akt1 on tumorigenesis and development, Akt1 was silenced by RNAi in the highly metastatic murine breast cancer 4T1 cells. Akt1 silencing didn't affect the proliferation of breast cancer cells in MTT assay, while reduced the migration in Transwell assay. Consistent with the above results, Akt1 silencing didn't change the primary tumor weight, but significantly suppressed lung metastasis of 4T1 cells. These observations indicated Akt1 plays an important role in murine breast cancer metastasis, and suggested that Akt1 might be a therapeutic target for breast cancer metastasis.

Key words: Akt1;Breast cancer;Migration;Tumor metastasis
收稿日期: 2008-11-07 出版日期: 2009-03-31
基金资助:

国家“973”基金

通讯作者: 于文功   
服务  
把本文推荐给朋友
加入引用管理器
E-mail Alert
RSS
作者相关文章  
刘海艳 顾玉超 宓文义 于文功

引用本文:

刘海艳,顾玉超,宓文义,于文功. Akt1基因沉默降低小鼠乳腺癌细胞的肺转移能力[J]. 中国生物工程杂志, 2009, 29(03): 14-19.

LIU Hai-Yan- Gu-Yu-Chao- Fu-Wen-Xi- Xu-Wen-Gong. Akt1 Silencing Inhibits Lung Metastasis of Murine Breast Cancer Cells. China Biotechnology, 2009, 29(03): 14-19.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/        https://manu60.magtech.com.cn/biotech/CN/Y2009/V29/I03/14

[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

No related articles found!