Triple-negative breast cancers express receptors for growth hormone-releasing hormone (GHRH) and respond to GHRH antagonists with growth inhibition

Abstract

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.