前列腺局限性Akt激活诱导的前列腺上皮内瘤变：MPAKT模型
Prostate intraepithelial neoplasia induced by prostate restricted Akt activation: the MPAKT model.
作者信息
Majumder Pradip K, Yeh Jen Jen, George Daniel J, Febbo Phillip G, Kum Jennifer, Xue Qi, Bikoff Rachel, Ma Hongfeng, Kantoff Philip W, Golub Todd R, Loda Massimo, Sellers William R
机构信息
Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
出版信息
Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7841-6. doi: 10.1073/pnas.1232229100. Epub 2003 Jun 10.
Abstract
To determine whether Akt activation was sufficient for the transformation of normal prostate epithelial cells, murine prostate restricted Akt kinase activity was generated in transgenic mice (MPAKT mice). Akt expression led to p70S6K activation, prostatic intraepithelial neoplasia (PIN), and bladder obstruction. mRNA expression profiles from MPAKT ventral prostate revealed similarities to human cancer and an angiogenic signature that included three angiogenin family members, one of which was found elevated in the plasma of men with prostate cancer. Thus, the MPAKT model may be useful in studying the role of Akt in prostate epithelial cell transformation and in the discovery of molecular markers relevant to human disease.
摘要
为了确定Akt激活是否足以使正常前列腺上皮细胞发生转化，在转基因小鼠（MPAKT小鼠）中产生了小鼠前列腺限制性Akt激酶活性。Akt表达导致p70S6K激活、前列腺上皮内瘤变（PIN）和膀胱梗阻。来自MPAKT腹侧前列腺的mRNA表达谱显示与人类癌症相似，并且具有血管生成特征，其中包括三个血管生成素家族成员，其中一个在前列腺癌男性的血浆中升高。因此，MPAKT模型可能有助于研究Akt在前列腺上皮细胞转化中的作用以及发现与人类疾病相关的分子标志物。
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本文引用的文献
1
Akt induces enhanced myocardial contractility and cell size in vivo in transgenic mice.
Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12333-8. doi: 10.1073/pnas.172376399.
2
Gene expression correlates of clinical prostate cancer behavior.
Cancer Cell. 2002 Mar;1(2):203-9. doi: 10.1016/s1535-6108(02)00030-2.
3
Prostatic intraepithelial neoplasia.
Curr Urol Rep. 2000 May;1(1):65-70. doi: 10.1007/s11934-000-0037-x.
4
Insulin stimulates hypoxia-inducible factor 1 through a phosphatidylinositol 3-kinase/target of rapamycin-dependent signaling pathway.
J Biol Chem. 2002 Aug 2;277(31):27975-81. doi: 10.1074/jbc.M204152200. Epub 2002 May 24.
5
Essential role of AKT-1/protein kinase B alpha in PTEN-controlled tumorigenesis.
Mol Cell Biol. 2002 Jun;22(11):3842-51. doi: 10.1128/MCB.22.11.3842-3851.2002.
6
Akt/protein kinase B promotes organ growth in transgenic mice.
Mol Cell Biol. 2002 Apr;22(8):2799-809. doi: 10.1128/MCB.22.8.2799-2809.2002.
7
Tumor induction by an Lck-MyrAkt transgene is delayed by mechanisms controlling the size of the thymus.
Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):14967-72. doi: 10.1073/pnas.231467698.
8
Islet beta cell expression of constitutively active Akt1/PKB alpha induces striking hypertrophy, hyperplasia, and hyperinsulinemia.
J Clin Invest. 2001 Dec;108(11):1631-8. doi: 10.1172/JCI13785.
9
Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses.
Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13790-5. doi: 10.1073/pnas.191502998. Epub 2001 Nov 13.
10
Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR.
Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10314-9. doi: 10.1073/pnas.171076798. Epub 2001 Aug 14.
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