Evidence that corticotropin-releasing hormone inhibits cell growth of human breast cancer cells via the activation of CRH-R1 receptor subtype.
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.
Graziani
Grazia
G
Pharmacology and Medical Oncology Section, Department of Neuroscience, University of Rome Tor Vergata, Rome, Italy.
Tentori
Lucio
L
Muzi
Alessia
A
Vergati
Matteo
M
Tringali
Giuseppe
G
Pozzoli
Giacomo
G
Navarra
Pierluigi
P
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
D006728:Hormones; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; C103016:antalarmin; D004958:Estradiol; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone