Proliferation-associated Brn-3b transcription factor can activate cyclin D1 expression in neuroblastoma and breast cancer cells

• Published in: Oncogene Vol. 27; no. 1; pp. 145 - 154
• Main Authors: Budhram-Mahadeo, V S, Irshad, S, Bowen, S, Lee, S A, Samady, L, Tonini, G P, Latchman, D S
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.01.2008; Nature Publishing; Nature Publishing Group
• Subjects: Apoptosis; Biological and medical sciences; Biopsy; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Brn-3 protein; Cancer cells; Cell Biology; Cell Line, Tumor; Cell physiology; Cell proliferation; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Chromatin; Cyclin D1; Cyclin D1 - biosynthesis; Cyclin D1 - genetics; Cyclin D1 - metabolism; DNA binding proteins; Electrophoretic mobility; Female; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation, Neoplastic; Genetic aspects; Genetics; Gynecology. Andrology. Obstetrics; Human Genetics; Humans; Immunoprecipitation; Internal Medicine; Mammary gland diseases; Medical sciences; Medicine; Medicine & Public Health; Molecular and cellular biology; Mutation; Neuroblastoma; Neuroblastoma - metabolism; Neuroblastoma - pathology; Neurology; Neurosciences; Oncology; Physiological aspects; RNA, Messenger - biosynthesis; RNA, Messenger - metabolism; short-communication; Site-directed mutagenesis; Transcription Factor Brn-3B - biosynthesis; Transcription Factor Brn-3B - genetics; Transcription Factor Brn-3B - physiology; Transcriptional Activation; Transfection; Tumor cell lines; Tumor Cells, Cultured; Tumors; Tumors of the nervous system. Phacomatoses; Up-Regulation - physiology; United Kingdom; neuroblastoma; breast cancer; cyclin D1; gene expression; Brn-3b; Cell proliferation; Nervous system diseases; Bm-3b; Breast cancer; Malignant tumor; Neuroblastoma; Cyclin D1; Gene expression; Carcinogenesis; Mammary gland diseases; Autonomic neuropathy; Transcription factor; Cancer
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1210621

Brn-3b transcription factor enhances proliferation of neuroblastoma (NB) and breast cancer cell lines in vitro and increases the rate and size of in vivo tumour growth, whereas reducing Brn-3b slows growth, both in vitro and in vivo . Brn-3b is elevated in >65% of breast cancer biopsies, and here we demonstrate that Brn-3b is also elevated in NB tumours. We show a significant correlation between Brn-3b and cyclin D1 (CD1) in breast cancers and NB tumours and cell lines. Brn-3b directly transactivates the CD1 promoter in co-transfection experiments, whereas electrophoretic mobility shift assay and chromatin immunoprecipitation assays demonstrate that Brn-3b protein binds to an octamer sequence located in the proximal CD1 promoter. Site-directed mutagenesis of this sequence resulted in loss of transactivation of the CD1 promoter by Brn-3b. Thus, Brn-3b may act to alter growth properties of breast cancer and NB cells by enhancing CD1 expression in these cells.