Expression of the IGF Axis Is Decreased in Local Prostate Cancer but Enhanced after Benign Prostate Epithelial Differentiation and TGF-β Treatment
Expression of the IGF Axis Is Decreased in Local Prostate Cancer but Enhanced after Benign Prostate Epithelial Differentiation and TGF-β Treatment
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DOI：
10.1016/j.ajpath.2011.08.026
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发表时间：
2011-12-01
影响因子：
6
通讯作者：
Klocker, Helmut
中科院分区：
文献类型：
--
作者：
Massoner, Petra;Rennau, Michael Ladurner;Klocker, Helmut
胰岛素样生长因子（IGF）轴是一种在癌症研究中被广泛研究的分子通路。针对不同肿瘤（包括前列腺癌）的IGI71受体（IGI-71R）的临床试验正在进行中。虽然IGI7轴在前列腺癌中的研究已经进入临床试验阶段，但IGF轴在良性前列腺和前列腺癌中的表达和功能作用还有待进一步明确。我们用定量PCR方法测定了局部前列腺癌显微解剖组织标本中IGI7轴mRNA的表达水平。IGF轴的所有成员，包括IG171、IGF2、IGF结合蛋白1至6和胰岛素受体，在前列腺间质室和上皮室中均被测量。与匹配的良性组织相比，IGF1、16172、IGF1R和胰岛素受体在前列腺癌局部组织中表达下调，提示IGF轴在前列腺癌发展过程中未被诱导。通过一个新的前列腺上皮分化模型，我们发现在正常前列腺上皮分化过程中，IGF轴的表达增强，并受肿瘤生长因子(TGF)- β的调节。我们的数据揭示了IGF轴在前列腺分化中的功能作用，强调了IGF轴在正常发育中的重要性，并强调了在进入高级临床试验之前准确靶点验证的重要性。（医学学报，2011,179:2905-2919;DOI: 10.1016/ j.j ajpath.2011.08.026）
The insulin-like growth factor (IGF) axis is a molecular pathway intensively investigated in cancer research. Clinical trials targeting the IGI71 receptor (IGI-71R) in different tumors, including prostate cancer, are under way. Although studies on the IGI7 axis in prostate cancer have already entered into clinical trials, the expression and functional role of the IGF axis in benign prostate and in prostate cancer needs to be better defined. We determined mRNA expression levels of the IGI7 axis in microdissected tissue specimens of local prostate cancer using quantitative PCR. All members of the IGF axis, including IG171, IGF2, IGF binding proteins 1 through 6, and insulin receptor, were measured in both the stromal and epithelial compartments of the prostate. IGF1, 16172, IGF1R, and insulin receptor were down-regulated in local prostate cancer tissue compared with matched benign tissue, suggesting that the IGF axis is not induced during prostate cancer development. Using a new prostate epithelial differentiation model, we demonstrate that the expression of the IGF axis is enhanced during normal prostate epithelial differentiation and regulated by tumor growth factor (TGF)-beta. Our data reveal a functional role of the IGF axis in prostate differentiation, underscoring the importance of the IGF axis in normal development and emphasizing the importance of accurate target validation before moving to advanced clinical trials. (Am J Puthol 2011, 179: 2905-2919; DOI: 10.1016/j.ajpath.2011.08.026)