Function of UDP-glucuronosyltransferase 2B17 (UGT2B17) is involved in endometrial cancer.
Endometrial cancer (EC) is a steroid hormone-dependent cancer. Uridine 5'-diphospho-glucuronosyltransferase enzymes conjugate and detoxify endogenous and exogenous steroid hormones and environmental carcinogens. Among these enzymes, the function of UGT2B17 is unknown except for glucuronidation. The messenger RNA expression of UGT2B17 and myeloid cell leukemia-1 (Mcl-1) was significantly increased in EC tissues compared with matched normal endometrial tissues. Therefore, we focused on the function of UGT2B17 in EC. A total of nine patients with confirmed EC were enrolled in this study to investigate the expression of UGT2B17 and target genes. EC cell lines were used for functional tests including cell growth, invasion, apoptosis and cell cycle analyses. To find the target genes of UGT2B17, we performed microarray analysis to see which genes were upregulated or downregulated by UGT2B17-transfected cells. Functional analysis showed decreased numbers of viable cells and increased numbers of apoptotic cells in si-UGT2B17-transfected Ishikawa cells. Among microarray target genes, Mcl-1 was significantly downregulated in si-UGT2B17-transfected cells. We also found upregulation of Puma protein, a target of Mcl-1, in si-UGT2B17-transfected cells. This is the first report to show that UGT2B17 and Mcl-1 expression are upregulated in EC tissues and that UGT2B17 depletion induces inhibition of cell growth and apoptosis in EC cells through Mcl-1 downregulation.
Hirata
Hiroshi
H
Department of Urology, Veterans Affairs Medical Center and University of California at San Francisco, 4150 Clement Street, San Francisco, CA 94121, USA.
Hinoda
Yuji
Y
Zaman
Mohd S
MS
Chen
Yi
Y
Ueno
Koji
K
Majid
Shahana
S
Tripsas
Christina
C
Rubin
Mary
M
Chen
Lee-May
LM
Dahiya
Rajvir
R
D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D016022:Case-Control Studies; D002448:Cell Adhesion; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D016889:Endometrial Neoplasms / Q000201:enzymology* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D005838:Genotype; D014453:Glucuronosyltransferase / Q000502:physiology*; D006801:Humans; D015778:Minor Histocompatibility Antigens; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D015778:Minor Histocompatibility Antigens; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014453:Glucuronosyltransferase; C500513:UGT2B17 protein, human