Identification of UDP-glucuronosyltransferase 1A10 in non-malignant and malignant human breast tissues.
UGT1A10 was recently identified as the major isoform that conjugates estrogens. In this study, real-time PCR revealed high levels of UGT1A10 and UGT2B7 mRNA in human breast tissues. The expression of UGT1A10 in breast was a novel finding. UGT1A10 and UGT2B7 mRNAs were differentially expressed among normal and malignant specimens. Their overall expression was significantly decreased in breast carcinomas as compared to normal breast specimens (UGT1A10: 68+/-26 vs. 252+/-86, respectively; p<0.05) and (UGT2B7: 1.4+/-0.7 vs. 12+/-4, respectively; p<0.05). Interestingly, in African American women, UGT1A10 expression was significantly decreased in breast carcinomas in comparison to normals (57+/-35 vs. 397+/-152, respectively; p<0.05). Among Caucasian women, UGT2B7 was significantly decreased in breast carcinomas in comparison to normals (1.1+/-0.5 vs. 13.5+/-6, respectively; p<0.05). Glucuronidation of 4-hydroxylated estrone (4-OHE(1)) was significantly reduced in breast carcinomas compared to normals (30+/-15 vs. 106+/-31, respectively; p<0.05). Differential down-regulation of UGT1A10 and UGT2B7 mRNAs, protein, and activity in breast carcinomas compared to the adjacent normal breast specimens from the same donor were also found. These data illustrate the novel finding of UGT1A10 in human breast and confirm the expression of UGT2B7. Significant individual variation and down-regulation of expression in breast carcinomas of both isoforms were also demonstrated. These findings provide evidence that decreased UGT expression and activity could result in the promotion of carcinogenesis.
Starlard-Davenport
Athena
A
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, 4301 West Markham, Slot 516, Little Rock, AR 72205, USA.
Lyn-Cook
Beverly
B
Radominska-Pandya
Anna
A
D001483:Base Sequence; D015153:Blotting, Western; D001940:Breast / Q000201:enzymology*; D001943:Breast Neoplasms / Q000201:enzymology*; D017931:DNA Primers; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics
D017931:DNA Primers; D012333:RNA, Messenger; C476725:bilirubin uridine-diphosphoglucuronosyl transferase 1A10; D014453:Glucuronosyltransferase