Department of Clinical and Experimental Medicine "G. Salvatore", University of Catanzaro "Magna Graecia", V.le Europa (Loc. Germaneto), 88100 Catanzaro, Italy.
PPAR Res. 2009;2009:571365. doi: 10.1155/2009/571365. Epub 2009 Jun 29.
The insulin receptor (IR) plays a crucial role in mediating the metabolic and proliferative functions triggered by the peptide hormone insulin. There is considerable evidence that abnormalities in both IR expression and function may account for malignant transformation and tumour progression in some human neoplasias, including breast cancer. PPARγ is a ligand-activated, nuclear hormone receptor implicated in many pleiotropic biological functions related to cell survival and proliferation. In the last decade, PPARγ agonists-besides their known action and clinical use as insulin sensitizers-have proved to display a wide range of antineoplastic effects in cells and tissues expressing PPARγ, leading to intensive preclinical research in oncology. PPARγ and activators affect tumours by different mechanisms, involving cell proliferation and differentiation, apoptosis, antiinflammatory, and antiangiogenic effects. We recently provided evidence that PPARγ and agonists inhibit IR by non canonical, DNA-independent mechanisms affecting IR gene transcription. We conclude that IR may be considered a new PPARγ "target" gene, supporting a potential use of PPARγ agonists as antiproliferative agents in selected neoplastic tissues that overexpress the IR.
胰岛素受体（IR）在介导肽激素胰岛素触发的代谢和增殖功能中起着至关重要的作用。有相当多的证据表明，IR 的表达和功能异常可能导致某些人类肿瘤（包括乳腺癌）的恶性转化和肿瘤进展。过氧化物酶体增殖物激活受体γ（PPARγ）是一种配体激活的核激素受体，与细胞存活和增殖相关的许多多效生物学功能有关。在过去的十年中，PPARγ 激动剂——除了作为胰岛素增敏剂的已知作用和临床用途外——已被证明在表达 PPARγ 的细胞和组织中具有广泛的抗肿瘤作用，这导致了肿瘤学领域的大量临床前研究。PPARγ 和激动剂通过不同的机制影响肿瘤，涉及细胞增殖和分化、细胞凋亡、抗炎和抗血管生成作用。我们最近提供的证据表明，PPARγ 和激动剂通过非典型的、不依赖于 DNA 的机制抑制 IR，从而影响 IR 基因转录。我们得出结论，IR 可以被认为是 PPARγ 的一个新的“靶”基因，支持将 PPARγ 激动剂作为选择性表达 IR 的肿瘤组织中的增殖抑制剂的潜在用途。
