title: Association of CYP39A1, RUNX2 and oxidized alpha-1 antitrypsin expression in relation to cholangiocarcinoma progression.
abstract: Cytochrome P450 (CYP) enzymes are a large family of constitutive and inducible mono-oxygenase enzymes that play a central role in the oxidative metabolism of both xenobiotic and endogenous compounds. Several CYPs are involved in metabolism of oxysterols, which are cholesterol oxidation products whose expression may be dysregulated in inflammation-related diseases including cancer. This study focused on CYP39A1, which can metabolize 24-hydroxycholesterol (24-OH) that plays important roles in the inflammatory response and oxidative stress. We aimed to investigate the expression status of CYP39A1 and its transcription factor (RUNX2) in relation to clinical significance in cholangiocarcinoma (CCAs) and to determine whether 24-OH could induce oxidative stress in CCA cell lines. Immunohistochemistry showed that 70% and 30% of CCA patients had low and high expression of CYP39A1, respectively. Low expression of CYP39A1 demonstrated a significant correlation with metastasis. Our results also revealed that the expression of RUNX2 had a positive correlation with CYP39A1. Low expression of both CYP39A1 (70%) and RUNX2 (37%) was significantly related with poor prognosis of CCA patients. Interestingly, oxidized alpha-1 antitrypsin (ox-A1AT), an oxidative stress marker, was significantly increased in CCA tissues in which CYP39A1 and RUNX2 were down regulated. Additionally, immunocytochemistry showed that 24-OH could induce ox-A1AT in CCA cell lines. In conclusion, our study revealed putative roles of the CYP39A1 enzyme in prognostic determination of CCAs.
authors.affiliation: Departments of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand E-mail : puangrat@kku.ac.th.
authors.forename: Chakkaphan
authors.initials: C
authors.lastname: Khenjanta
authors.forename: Raynoo
authors.initials: R
authors.lastname: Thanan
authors.forename: Apinya
authors.initials: A
authors.lastname: Jusakul
authors.forename: Anchalee
authors.initials: A
authors.lastname: Techasen
authors.forename: Wassana
authors.initials: W
authors.lastname: Jamnongkan
authors.forename: Nisana
authors.initials: N
authors.lastname: Namwat
authors.forename: Watcharin
authors.initials: W
authors.lastname: Loilome
authors.forename: Chawalit
authors.initials: C
authors.lastname: Pairojkul
authors.forename: Puangrat
authors.initials: P
authors.lastname: Yongvanit
mesh_terms: D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000473:pathology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011379:Prognosis; D013250:Steroid Hydroxylases / Q000378:metabolism*; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D006888:Hydroxycholesterols; C493709:RUNX2 protein, human; D000515:alpha 1-Antitrypsin; C044563:24-hydroxycholesterol; D013250:Steroid Hydroxylases; C499573:CYP39A1 protein, human