title: 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.
authors.affiliation: Department of Gynecology and Obstetrics, University of Lübeck, Lübeck, Germany. frank.koester@uk-sh.de
authors.forename: Frank
authors.initials: F
authors.lastname: Köster
authors.forename: Jörg B
authors.initials: JB
authors.lastname: Engel
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Schally
authors.forename: Arnd
authors.initials: A
authors.lastname: Hönig
authors.forename: Andreas
authors.initials: A
authors.lastname: Schröer
authors.forename: Stephan
authors.initials: S
authors.lastname: Seitz
authors.forename: Florian
authors.initials: F
authors.lastname: Hohla
authors.forename: Olaf
authors.initials: O
authors.lastname: Ortmann
authors.forename: Klaus
authors.initials: K
authors.lastname: Diedrich
authors.forename: Stefan
authors.initials: S
authors.lastname: Buchholz
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017337:Sermorelin / Q000494:pharmacology*
chemical_list: C501461:MZ-J-7-118; D012333:RNA, Messenger; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D017337:Sermorelin; D048049:Extracellular Signal-Regulated MAP Kinases; C048250:somatotropin releasing hormone receptor