Köster Frank, Engel Jörg B, Schally Andrew V, Hönig Arnd, Schröer Andreas, Seitz Stephan, Hohla Florian, Ortmann Olaf, Diedrich Klaus, Buchholz Stefan
Department of Gynecology and Obstetrics, University of Lübeck, Lübeck, Germany.
Breast Cancer Res Treat. 2009 Jul;116(2):273-9. doi: 10.1007/s10549-008-0120-4. Epub 2008 Jul 16.
Triple-negative breast cancers do not express receptors for estrogen or progesterone and do not overexpress HER2. These tumors have an unfavorable prognosis and at present chemotherapy is the only treatment option. Because the antagonists of growth hormone-releasing hormone (GHRH) have been shown to inhibit growth of a variety of cancers by endocrine and paracrine/autocrine mechanisms, we evaluated the expression of GHRH receptors in human specimens of triple-negative breast cancers and the response to GHRH by in vitro models. In samples of triple-negative breast cancers we found mRNA expression for the GHRH receptor and its functional splice variant SV1 in 25 and 70% of the cases, respectively and for GHRH in 80% of the samples. Immunoreaction of SV1 was detected in the human triple-negative breast cancer cell line HCC1806 while HCC1937 was negative. The growth of HCC1806 was stimulated by GHRH(1-44)NH(2) and inhibited by GHRH antagonist MZ-J-7-118. In addition, in HCC1806 MAP-kinases ERK-1/2 were activated by GHRH. Our findings suggest the existence of an autocrine loop consisting of GHRH and GHRH receptors in triple-negative breast cancers. Our in vitro studies demonstrate that targeting the GHRH receptor may be a therapeutic option which should be evaluated in studies in vivo.
三阴性乳腺癌不表达雌激素或孕激素受体，也不过表达HER2。这些肿瘤预后不良，目前化疗是唯一的治疗选择。由于生长激素释放激素（GHRH）拮抗剂已被证明可通过内分泌和旁分泌/自分泌机制抑制多种癌症的生长，我们评估了三阴性乳腺癌人体标本中GHRH受体的表达以及体外模型对GHRH的反应。在三阴性乳腺癌样本中，我们分别在25%和70%的病例中发现了GHRH受体及其功能性剪接变体SV1的mRNA表达，在80%的样本中发现了GHRH的mRNA表达。在人三阴性乳腺癌细胞系HCC1806中检测到SV1的免疫反应，而HCC1937为阴性。GHRH(1-44)NH(2)刺激HCC1806的生长，而GHRH拮抗剂MZ-J-7-118抑制其生长。此外，在HCC1806中，GHRH激活了丝裂原活化蛋白激酶ERK-1/2。我们的研究结果表明，三阴性乳腺癌中存在由GHRH和GHRH受体组成的自分泌环路。我们的体外研究表明，靶向GHRH受体可能是一种治疗选择，应在体内研究中进行评估。
