Hypoxia enhances MUC1 expression in a lung adenocarcinoma cell line.
Expression of a transmembrane mucin MUC1 is emphasized in most cases of carcinoma. High expression of MUC1 is closely associated with cancer progression and metastasis, leading to poor prognosis. However, little is known about how MUC1 is overexpressed in malignant tumor. In this study, we demonstrated that: (1) Hypoxia, a typical feature of malignant tumor, enhanced the expression of MUC1 mRNA and protein in a human lung adenocarcinoma cell line; (2) the hypoxia-induced increase in MUC1 mRNA was mediated by the transcriptional activity of MUC1 promoter, but not mRNA stability. Moreover; (3) CoCl(2), an inducer of Hypoxia Inducible Factor (HIF)-1alpha, increased the expression of MUC1 mRNA; and (4) HIF-1alpha-targeted siRNA but not its control siRNA decreased hypoxia-induced MUC1 mRNA. These data suggest that hypoxia enhances the expression of MUC1 through the transcriptional regulation by HIF-1alpha in a human lung epithelial cell line.
Mikami
Yuji
Y
Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto City, Kumamoto 862-0973, Japan.
Hisatsune
Akinori
A
Tashiro
Tomomi
T
Isohama
Yoichiro
Y
Katsuki
Hiroshi
H
D000230:Adenocarcinoma / Q000235:genetics*; D015687:Cell Hypoxia / Q000235:genetics; D045744:Cell Line, Tumor; D003035:Cobalt / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics*; D018396:Mucin-1 / Q000235:genetics*; D011401:Promoter Regions, Genetic; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D014158:Transcription, Genetic
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C060192:MUC1 protein, human; D018396:Mucin-1; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D003035:Cobalt; C018021:cobaltous chloride