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: Tomomi Yoda, Kyoko Kikuchi, Yasuhiro Miki, Yoshiaki Onodera, Shuko Hata, Kiyoshi Takagi, Yasuhiro Nakamura, Hisashi Hirakawa, Takanori Ishida, Takashi Suzuki, Noriaki Ohuchi, Hironobu Sasano, Keely May McNamara
• Journal: Molecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 413 Pg. 236-47 (Sep 15 2015) ISSN: 1872-8057 [Electronic] Ireland
• PMID: 26170067 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Neoplasm Proteins
• Receptors, Prostaglandin
• SNAI1 protein, human
• Snail Family Transcription Factors
• Transcription Factors
• prostaglandin F2alpha receptor
• Dinoprost
• 3-Hydroxysteroid Dehydrogenases
• Hydroxyprostaglandin Dehydrogenases
• AKR1C3 protein, human
• Aldo-Keto Reductase Family 1 Member C3

Topics

• 3-Hydroxysteroid Dehydrogenases (genetics, metabolism)
• Adult
• Aged
• Aged, 80 and over
• Aldo-Keto Reductase Family 1 Member C3
• Breast Neoplasms (genetics, metabolism, pathology)
• Catalysis
• Dinoprost (genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Hydroxyprostaglandin Dehydrogenases (genetics, metabolism)
• Middle Aged
• Neoplasm Proteins (genetics, metabolism)
• Receptors, Prostaglandin (genetics, metabolism)
• Snail Family Transcription Factors
• Transcription Factors (biosynthesis, genetics)