title: Evidence that corticotropin-releasing hormone inhibits cell growth of human breast cancer cells via the activation of CRH-R1 receptor subtype.
abstract: It has been previously shown that corticotropin-releasing hormone (CRH) exerts antiproliferative activity on an estrogen-dependent tumor cell line, i.e. human endometrial adenocarcinoma Ishikawa (IK) cells. Here we have investigated the effects of CRH on another estrogen-dependent tumor cell line, human breast cancer MCF7 cells. In this paradigm, CRH given at a fixed concentration of 100 nM significantly inhibited cell growth induced by 100 nM estradiol (E2) after 48 and 72 h of incubation. This effect was not associated with the induction of apoptosis. CRH inhibition of cell proliferation was counteracted in a concentration-dependent manner by the non-selective CRH receptor antagonist, astressin, as well as by a CRH-R1 selective receptor antagonist, antalarmin. RNase protection assays carried out on MCF7 under basal conditions showed that these cells express in a constitutive manner the CRH-R1 receptor subtype. We have also investigated the putative source of CRH acting on breast cancer cells; we found that MCF7 cells express CRH mRNA under basal conditions and secrete sizable amounts of immunoreactive CRH, which leads to postulate the existence of paracrine-autocrine inhibitory mechanism operated by CRH in breast cancer cells.
authors.affiliation: Pharmacology and Medical Oncology Section, Department of Neuroscience, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Graziani
authors.forename: Lucio
authors.initials: L
authors.lastname: Tentori
authors.forename: Alessia
authors.initials: A
authors.lastname: Muzi
authors.forename: Matteo
authors.initials: M
authors.lastname: Vergati
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tringali
authors.forename: Giacomo
authors.initials: G
authors.lastname: Pozzoli
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Navarra
mesh_terms: D019898:Autocrine Communication / Q000187:drug effects*; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006728:Hormones / Q000494:pharmacology*; D006801:Humans; D019899:Paracrine Communication / Q000187:drug effects*; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000099052:CRF Receptor, Type 1
chemical_list: D006728:Hormones; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; C103016:antalarmin; D004958:Estradiol; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone