title: Involvement of the NF-кB/p50/Bcl-3 complex in response to antiangiogenic therapy in a mouse model of metastatic renal cell carcinoma.
abstract: Renal cell carcinoma (RCC) represents approximately 2-3% of human malignancies. Nuclear transcription factor кB (NF-кB) is composed of a family of transcription factors that have been associated with the development and progression of RCC. Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. In this study, we evaluated the expression of NF-кB in metastatic tumor cells from animals treated with ES. Balb/c-bearing Renca-EGFP cells were treated with NIH/3T3-LendSN or NIH/3T3-LXSN cells as a control. At the end of the in vivo experiment, plasma Renca-EGFP-sorted cells and tissue lung samples were collected. A real-time PCR array for NF-κB target genes revealed that ES therapy led to down regulation of Bcl-3 (P<0.031), NF-кB1 (P<0.001) and c-Rel (P<0.004) in the ES-treated group. Using an electrophoretic mobility shift assay (EMSA), we observed a reduction in NF-kB binding activity in ES-treated Renca-EGP cells. Furthermore, a supershift assay showed a clear shift of the NF-кB DNA band in samples incubated with a p50 antibody. By immunohistochemistry analysis, ES treatment resulted in a significant reduction in expression of p50. (ES vs. control P<0.05). The immunoprecipitation experiments confirmed the presence of a p50/Bcl-3 complex in nuclear extracts from cells of metastatic lung tissues. Our findings indicate that p50 and Bcl-3 plays a regulatory role in gene transcription in RCC.
authors.affiliation: Nephrology Division, Federal University of Sao Paulo, Sao Paulo, Brazil; Biotechnology Department, IPEN-CNEN, Sao Paulo, Brazil.
authors.forename: Marina
authors.initials: M
authors.lastname: de Souza Braga
authors.affiliation: Department of Oral Pathology,Dental School, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Katiúcia Batista
authors.initials: KB
authors.lastname: da Silva Paiva
authors.affiliation: Nephrology Division, Federal University of Sao Paulo, Sao Paulo, Brazil; Biotechnology Department, IPEN-CNEN, Sao Paulo, Brazil.
authors.forename: Karen
authors.initials: K
authors.lastname: Foguer
authors.affiliation: Nephrology Division, Federal University of Sao Paulo, Sao Paulo, Brazil; Biotechnology Department, IPEN-CNEN, Sao Paulo, Brazil.
authors.forename: Karen Cristina
authors.initials: KC
authors.lastname: Barbosa Chaves
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Larissa
authors.initials: L
authors.lastname: de Sá Lima
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Cristoforo
authors.initials: C
authors.lastname: Scavone
authors.affiliation: Nephrology Division, Federal University of Sao Paulo, Sao Paulo, Brazil; Biotechnology Department, IPEN-CNEN, Sao Paulo, Brazil. Electronic address: mhmarumo@terra.com.br.
authors.forename: Maria Helena
authors.initials: MH
authors.lastname: Bellini
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000081242:B-Cell Lymphoma 3 Protein; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism; D002460:Cell Line; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D043169:Endostatins / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D052002:NF-kappa B p50 Subunit / Q000378:metabolism*; D041681:NIH 3T3 Cells; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; C000631345:Bcl3 protein, mouse; D043169:Endostatins; D052002:NF-kappa B p50 Subunit; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors
keywords: Bcl-3; Endostatin; NF-кB; Renal cell carcinoma; p50