title: Transcript level of AKR1C3 is down-regulated in gastric cancer.
abstract: Steroid hormones have been shown to play a role in gastric carcinogenesis. Large amounts of steroid hormones are locally produced in the peripheral tissues of both genders. Type 5 of 17β-hydroxysteroid dehydrogenase, encoded by the AKR1C3 gene, plays a pivotal role in both androgen and estrogen metabolism, and its expression was found to be deregulated in different cancers. In this study we measured AKR1C3 transcript and protein levels in nontumoral and primary tumoral gastric tissues, and evaluated their association with some clinicopathological features of gastric cancer (GC). We found decreased levels of AKR1C3 transcript (p < 0.0001) and protein (p = 0.0021) in GC tissues compared with the adjacent, apparently histopathologically normal, mucosa. Lower levels of AKR1C3 transcript were observed in diffuse and intestinal types of GC, whereas AKR1C3 protein levels were decreased in tumors with multisite localization, in diffuse histological type, T3, T4, and G3 grades. We also determined the effect of the histone deacetylase inhibitor sodium butyrate (NaBu) on AKR1C3 expression in EPG 85-257 and HGC-27 GC cell lines. We found that NaBu elevates the levels of both AKR1C3 transcript and protein in the cell lines we investigated. Together, our results suggest that decreased expression of AKR1C3 may be involved in development of GC and can be restored by NaBu.
authors.affiliation: a Department of Biochemistry and Molecular Biology, University of Medical Sciences, Poznań, Poland.
authors.forename: Bartosz Adam
authors.initials: BA
authors.lastname: Frycz
authors.affiliation: b First Department of Surgical Oncology and General Surgery, Greater Poland Cancer Centre, Poznań, Poland.|c Regional Specialist Hospital, Research and Development Centre, Wrocław, Poland.
authors.forename: Dawid
authors.initials: D
authors.lastname: Murawa
authors.affiliation: d Department of General, Endocrinological Surgery and Gastroenterological Oncology, University of Medical Sciences, Poznań, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Borejsza-Wysocki
authors.affiliation: b First Department of Surgical Oncology and General Surgery, Greater Poland Cancer Centre, Poznań, Poland.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Wichtowski
authors.affiliation: b First Department of Surgical Oncology and General Surgery, Greater Poland Cancer Centre, Poznań, Poland.
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Spychała
authors.affiliation: d Department of General, Endocrinological Surgery and Gastroenterological Oncology, University of Medical Sciences, Poznań, Poland.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Marciniak
authors.affiliation: b First Department of Surgical Oncology and General Surgery, Greater Poland Cancer Centre, Poznań, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Murawa
authors.affiliation: d Department of General, Endocrinological Surgery and Gastroenterological Oncology, University of Medical Sciences, Poznań, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Drews
authors.affiliation: a Department of Biochemistry and Molecular Biology, University of Medical Sciences, Poznań, Poland.
authors.forename: Paweł Piotr
authors.initials: PP
authors.lastname: Jagodziński
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics*; D000368:Aged; D000074425:Aldo-Keto Reductase Family 1 Member C3; D020148:Butyric Acid / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000235:genetics*; D008297:Male; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D020148:Butyric Acid; D015096:3-Hydroxysteroid Dehydrogenases; D006911:Hydroxyprostaglandin Dehydrogenases; C487341:AKR1C3 protein, human; D000074425:Aldo-Keto Reductase Family 1 Member C3
keywords: AKR1C3; butyrate de sodium; cancer gastrique; enzymes stéroïdogéniques; gastric cancer; sodium butyrate; steroidogenesis; steroidogenic enzymes; stéroïdogenèse