TGF-beta upregulates tumor-associated carbonic anhydrase IX gene expression in Hep3B cells.
Carbonic anhydrase IX (CAIX) is a membrane-associated carbonic anhydrase (CA) that is overexpressed in a variety of tumor types and associated with increased metastasis, giving a poor prognosis. Transcriptional regulation of transmembrane protein CAIX is complex. We describe further characterization of the 1.2kb hCA9 promoter, and the effect of TGF-beta on the transcriptional activity and expression of hCAIX in Hep3B cells. Transcriptional activity of different promoter regions of hCA9 promoter showed the presence of negative regulatory region between -300bp and -500bp of hCAIX promoter. The -116/+38 region was enough for basal transcriptional activity in Hep3B cells. TGF-beta upregulates all promoter regions of hCA9 with the highest beig for -466/+38 that has a negatively regulated region. The transcriptional activation of hCA9 promoter by TGF-beta is consistent with hCAIX mRNA levels revealed by RT-PCR and hCAIX protein expression levels by flow cytometry in Hep3B cells.
Yildirim
Hatice
H
Department of Biology, Faculty of Art and Science, Balikesir University, 10145 Balikesir, Turkey.
Köçkar
Feray
F
D000951:Antigens, Neoplasm / Q000235:genetics*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics; D045744:Cell Line, Tumor; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000187:drug effects; D015533:Transcriptional Activation; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics / Q000502:physiology
D000951:Antigens, Neoplasm; D051793:Hypoxia-Inducible Factor 1; D016212:Transforming Growth Factor beta; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases