Tags

Type your tag names separated by a space and hit enter

Transforming growth factor beta 1 stimulates vascular endothelial growth factor gene transcription in human cholangiocellular carcinoma cells.
Cancer Res. 2003 Mar 01; 63(5):1083-92.CR

Abstract

The expression pattern and functional interaction of proangiogenic factors in human cholangiocellular carcinoma (CCC) have not been fully defined. We therefore investigated the expression of vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-beta 1 as well as their respective receptors in human CCC tumor samples and further analyzed their functional interaction in vitro. Expression of VEGF, TGF-beta 1, and their receptors was examined by immunohistochemistry, in situ hybridization, quantitative competitive reverse transcription-PCR, and ELISA. VEGF promoter analysis and identification of transcription factors involved in promoter regulation were investigated using transient transfection and electrophoretic mobility shift assays. We observed strong expression of VEGF in CCC tumor cells and localization of VEGF receptors 1 and 2 in endothelial cells; in addition, coexpression of TGF-beta 1 and its receptors in tumor cells suggests a possible functional interaction between both cytokines. In vitro studies confirmed a paracrine/autocrine stimulation of VEGF by TGF-beta 1 at a transcriptional level. Additional molecular studies using 5' deletion and mutational analysis of the human VEGF promoter revealed that TGF-beta 1 stimulates VEGF through Sp1-dependent transcriptional activation. These data suggest that overexpression and functional interaction of TGF-beta 1 and VEGF might contribute to the "angiogenic switch" and the malignant phenotype in human CCC.

Authors+Show Affiliations

Department of General Visceral and Transplantation Surgery, Charité, Humboldt-University, 13353 Berlin, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12615726

Citation

Benckert, Christoph, et al. "Transforming Growth Factor Beta 1 Stimulates Vascular Endothelial Growth Factor Gene Transcription in Human Cholangiocellular Carcinoma Cells." Cancer Research, vol. 63, no. 5, 2003, pp. 1083-92.
Benckert C, Jonas S, Cramer T, et al. Transforming growth factor beta 1 stimulates vascular endothelial growth factor gene transcription in human cholangiocellular carcinoma cells. Cancer Res. 2003;63(5):1083-92.
Benckert, C., Jonas, S., Cramer, T., Von Marschall, Z., Schäfer, G., Peters, M., Wagner, K., Radke, C., Wiedenmann, B., Neuhaus, P., Höcker, M., & Rosewicz, S. (2003). Transforming growth factor beta 1 stimulates vascular endothelial growth factor gene transcription in human cholangiocellular carcinoma cells. Cancer Research, 63(5), 1083-92.
Benckert C, et al. Transforming Growth Factor Beta 1 Stimulates Vascular Endothelial Growth Factor Gene Transcription in Human Cholangiocellular Carcinoma Cells. Cancer Res. 2003 Mar 1;63(5):1083-92. PubMed PMID: 12615726.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transforming growth factor beta 1 stimulates vascular endothelial growth factor gene transcription in human cholangiocellular carcinoma cells. AU - Benckert,Christoph, AU - Jonas,Sven, AU - Cramer,Thorsten, AU - Von Marschall,Zofia, AU - Schäfer,Georgia, AU - Peters,Michael, AU - Wagner,Karola, AU - Radke,Cornelia, AU - Wiedenmann,Bertram, AU - Neuhaus,Peter, AU - Höcker,Michael, AU - Rosewicz,Stefan, PY - 2003/3/5/pubmed PY - 2003/4/2/medline PY - 2003/3/5/entrez SP - 1083 EP - 92 JF - Cancer research JO - Cancer Res VL - 63 IS - 5 N2 - The expression pattern and functional interaction of proangiogenic factors in human cholangiocellular carcinoma (CCC) have not been fully defined. We therefore investigated the expression of vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-beta 1 as well as their respective receptors in human CCC tumor samples and further analyzed their functional interaction in vitro. Expression of VEGF, TGF-beta 1, and their receptors was examined by immunohistochemistry, in situ hybridization, quantitative competitive reverse transcription-PCR, and ELISA. VEGF promoter analysis and identification of transcription factors involved in promoter regulation were investigated using transient transfection and electrophoretic mobility shift assays. We observed strong expression of VEGF in CCC tumor cells and localization of VEGF receptors 1 and 2 in endothelial cells; in addition, coexpression of TGF-beta 1 and its receptors in tumor cells suggests a possible functional interaction between both cytokines. In vitro studies confirmed a paracrine/autocrine stimulation of VEGF by TGF-beta 1 at a transcriptional level. Additional molecular studies using 5' deletion and mutational analysis of the human VEGF promoter revealed that TGF-beta 1 stimulates VEGF through Sp1-dependent transcriptional activation. These data suggest that overexpression and functional interaction of TGF-beta 1 and VEGF might contribute to the "angiogenic switch" and the malignant phenotype in human CCC. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/12615726/Transforming_growth_factor_beta_1_stimulates_vascular_endothelial_growth_factor_gene_transcription_in_human_cholangiocellular_carcinoma_cells_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=12615726 DB - PRIME DP - Unbound Medicine ER -