title: 11β-Prostaglandin F2α, a bioactive metabolite catalyzed by AKR1C3, stimulates prostaglandin F receptor and induces slug expression in breast cancer.
abstract: Prostaglandins are a group of lipid compounds involved in inflammation and cancer. We focused on PGF2α and its stereoisomer 11β-PGF2α and examined the expression and functions of their cognate receptor (FP receptor) and metabolizing enzymes (AKR1B1 and AKR1C3 respectively) in breast cancer. In immunohistochemical analysis FP receptor status associated with adverse clinical outcome only in the AKR1C3 positive cases. Therefore, we studied FP receptor-mediated functions of 11β-PGF2α using FP receptor expressed MCF-7 cell line (MCF-FP). 11β-PGF2α treatment phosphorylated ERK and CREB and induced Slug expression through FP receptor in MCF-FP, and MCF-FP cells demonstrated decreased chemosensitivity compared to parental controls. Finally, the correlation between FP receptor and Slug was also confirmed immunohistochemically in breast cancer cases. Overall these results indicated that the actions of AKR1C3 can produce FP receptor ligands whose activation results in carcinoma cell survival in breast cancer.
authors.affiliation: Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Yoda
authors.affiliation: Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Kikuchi
authors.affiliation: Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miki
authors.affiliation: Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Onodera
authors.affiliation: Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Shuko
authors.initials: S
authors.lastname: Hata
authors.affiliation: Department of Pathology and Histotechnology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takagi
authors.affiliation: Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Tohoku Kosai Hospital, Sendai, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hirakawa
authors.affiliation: Department of Surgery, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Ishida
authors.affiliation: Department of Pathology and Histotechnology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Surgery, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Ohuchi
authors.affiliation: Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.affiliation: Department of Pathology, Tohoku University School of Medicine, Sendai, Japan. Electronic address: kmcnamara@patholo2.med.tohoku.ac.jp.
authors.forename: Keely May
authors.initials: KM
authors.lastname: McNamara
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000074425:Aldo-Keto Reductase Family 1 Member C3; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002384:Catalysis; D015237:Dinoprost / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000235:genetics / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D009363:Neoplasm Proteins; D011982:Receptors, Prostaglandin; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C034671:prostaglandin F2alpha receptor; D015237:Dinoprost; D015096:3-Hydroxysteroid Dehydrogenases; D006911:Hydroxyprostaglandin Dehydrogenases; C487341:AKR1C3 protein, human; D000074425:Aldo-Keto Reductase Family 1 Member C3
keywords: 11β-Prostaglandin F2α; Aldo-keto reductase family 1 member C3; Breast cancer; In vitro models; Pathology; Prostaglandin F receptor; Slug