Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor

G. D. Bella, R. Scanferlato, B. Colori
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引用次数: 2

Abstract

Background: The interaction between pituitary hormones (Growth Hormone-Prolactin), ovarian hormones (Estradiol) and growth factors forms the basis of the mechanisms underlying the growth of tumors of the breast. The literature contains reports of the increased expression of the mitogenic GH (Growth Hormone)/IGF1 (Insulin-Like Growth Factor) axis in tumor tissues compared to healthy tissues, with a directly proportional dose-dependent relationship between GH/IGF1, proliferative index and invasive ability in numerous types of tumors. Methods and Findings: We carried out this experimental research on the mitogenic role of GH and consequently on the rationale of the anticancer use of its inhibition. The levels of expression of several genes, GH and GHR, were evaluated in 39 cases of breast cancer, divided according to different risk levels on the basis of immunohistochemical and histological tests with nuclear grade. Conclusion: Research showed that breast cancers with a high and intermediate risk of recurrence are characterized by over-expression of GH and of its receptor (GHR). The expression was limited in cases with a low risk. The overexpression of GH-GHR in breast cancer with a ratio proportional to the level of aggressiveness is a rationale that can encourage a therapeutic intervention with inhibition of the mitogenic GH-IGF1-PRL axis and estrogen.
GH/GHR在乳腺癌中的过度表达及生长抑素作为生理抑制剂的抑癌作用
背景:垂体激素(生长激素-催乳素)、卵巢激素(雌二醇)和生长因子之间的相互作用构成了乳腺肿瘤生长机制的基础。文献报道,与健康组织相比,肿瘤组织中有丝分裂GH(生长激素)/IGF1(胰岛素样生长因子)轴的表达增加,在许多类型的肿瘤中,GH/IGF1、增殖指数和侵袭能力之间存在成正比的剂量依赖关系。方法和发现:我们对生长激素的有丝分裂作用进行了实验研究,从而探讨了利用生长激素抑制肿瘤的基本原理。对39例乳腺癌患者的GH、GHR基因表达水平进行评价,并在免疫组化和核分级组织学检查的基础上,根据不同的危险程度进行分级。结论:研究表明,GH及其受体(GHR)的过度表达是高、中复发风险乳腺癌的特征。这种表达在低风险的病例中是有限的。GH-GHR在乳腺癌中的过度表达与侵袭性水平成正比,这是鼓励抑制有丝分裂GH-IGF1-PRL轴和雌激素的治疗干预的基本原理。
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