Chhabra Yash, Waters Michael J, Brooks Andrew J
a The University of Queensland, Institute for Molecular Bioscience, Brisbane, Qld 4072, Australia.
b
Expert Rev Endocrinol Metab. 2011 Jan;6(1):71-84. doi: 10.1586/eem.10.73.
A substantial body of evidence supports a role for the growth hormone (GH)-IGF-1 axis in cancer incidence and progression. This includes epidemiological evidence relating elevated plasma IGF-1 to cancer incidence as well as a lack of cancers in GH/IGF-1 deficiency. Rodent models lacking GH or its receptor are strikingly resistant to the induction of a wide range of cancers, and treatment with the GH antagonist pegvisomant slows tumor progression. While GH receptor expression is elevated in many cancers, autocrine GH is present in several types, and overexpression of autocrine GH can induce cell transformation. While the mechanism of autocrine action is not clear, it does involve both STAT5 and STAT3 activation, and probably nuclear translocation of the GH receptor. Development of a more potent GH receptor antagonist or secretion inhibitor is warranted for cancer therapy.
大量证据支持生长激素（GH）-胰岛素样生长因子-1（IGF-1）轴在癌症发生和进展中起作用。这包括将血浆IGF-1升高与癌症发病率相关的流行病学证据，以及生长激素/胰岛素样生长因子-1缺乏时癌症的缺失。缺乏生长激素或其受体的啮齿动物模型对多种癌症的诱导具有显著抗性，生长激素拮抗剂培维索孟治疗可减缓肿瘤进展。虽然生长激素受体在许多癌症中表达升高，但自分泌生长激素存在于几种类型中，自分泌生长激素的过表达可诱导细胞转化。虽然自分泌作用机制尚不清楚，但它确实涉及STAT5和STAT3的激活，可能还涉及生长激素受体的核转位。开发更有效的生长激素受体拮抗剂或分泌抑制剂对癌症治疗是必要的。
