title: Role of corticotropin-releasing hormone family peptides in androgen receptor and vitamin D receptor expression and translocation in human breast cancer MCF-7 cells.
abstract: The presence of corticotropin-releasing hormone (CRH) in breast cancer biopsies suggests that it may play a role in the development of breast cancer. Here, the role of CRH in apoptosis and the relevant mechanisms were investigated. The CRH homologues, Urocortins, which have equal affinity for both corticotropin-releasing hormone receptor types 1 and 2, were secreted in MCF-7 breast cancer cells. CRH (receptor type 1 agonist) and Urocortin2 (receptor type 2 agonist) were used to substitute Urocortin to identify the differences between the two receptors. The results showed that both CRH and Urocortin2 promoted apoptosis of MCF-7 cells by regulating expressions and distributions of androgen receptor and vitamin D receptor. CRH down-regulated androgen receptor mRNA through inducing its decay while up-regulating androgen receptor protein expression and promoting nuclear transportation. Urocortin2 repressed the mRNA production of androgen receptor but had no significant impact on its protein expression. Both CRH and Urocortin2 time-dependently increased the protein expression of vitamin D receptor which translocated into the nuclei to realize its genic activity thereafter. The activity of CRH and Urocortin2 could be inhibited by Antalarmin and Antisauvagine-30, respectively. Additional analyses showed that CRH and Urocortin2 both phosphorylated heat shock protein 27, and this phosphorylation was associated with the nuclear transportation of vitamin D receptor. In conclusion, the results firstly revealed that CRH and Urocortin2 could induce breast cancer cell apoptosis via the two different receptors. The mechanisms involve phosphorylation of heat shock protein 27, the increment of androgen receptor and vitamin D receptor protein expression and their nuclear translocation.
authors.affiliation: Jiangsu Provincial Key Lab of Cardiovascular Diseases and Molecular Intervention, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Lai
authors.initials: L
authors.lastname: Jin
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.forename: Rui
authors.initials: R
authors.lastname: Guo
authors.forename: Rong
authors.initials: R
authors.lastname: Wan
authors.forename: Shengnan
authors.initials: S
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D021381:Protein Transport / Q000187:drug effects; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism*; D018167:Receptors, Calcitriol / Q000378:metabolism*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D054832:Urocortins / Q000494:pharmacology
chemical_list: D055551:HSP27 Heat-Shock Proteins; D012333:RNA, Messenger; D011944:Receptors, Androgen; D018167:Receptors, Calcitriol; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D003346:Corticotropin-Releasing Hormone