Type

Journal Article

Authors

Leonie S Young
Arnold D K Hill
Niamh Cosgrave

Subjects

Biochemistry

Topics
microtubule associated proteins drug effects proto oncogene proteins c myc cell line tumor breast neoplasms up regulation molecular sequence data transcription genetic inhibitor of apoptosis proteins pharmacology metabolism rna messenger promoter regions genetic humans birc5 protein human fibroblast growth factor 2 base sequence neoplasm proteins gene expression regulation neoplastic genetics

Growth factor-dependent regulation of survivin by c-myc in human breast cancer. (2006)

Abstract Survivin has emerged as a unique regulator of cell death through its response to growth factors, such as basic fibroblast growth factor (bFGF), which we have previously shown to be mitogen-activated protein kinase (MAPK) dependent. The transcriptional complex myc/max is an oncogene that lies downstream of the MAPK pathway, suggesting a possible role in survivin's regulation. In this study, we investigated the ability of bFGF to induce signalling of the MAPK effector transcription factor c-myc in human breast cancer. Treatment of SK-BR-3 breast cancer cell line with growth factor induced survivin expression and recruitment of c-myc to its response element in the promoter region of the target gene survivin as demonstrated by electromobility shift analysis and chromatin immunoprecipitation assays. The promoter region of survivin was assessed using bioinformatic techniques and DNA footprinting. Overexpression of c-myc increased survivin protein expression. This effect was eliminated when siRNA against c-myc was transfected into the cells. c-Myc drove transcriptional activity of survivin when transfected into SK-BR-3 cells with a luciferase reporter vector harbouring the c-myc response element specific for survivin. Using confocal fluorescent microscopy, myc was located to the nucleus of breast tumour epithelial cells and was found to be significantly associated with survivin (P < 0.0001). These data provide evidence that growth factors can signal through the transcription factor c-myc in human breast cancer. They also indicate a role for c-myc in the transcriptional regulation of survivin in breast cancer.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Leonie S Young, Arnold D K Hill, Niamh Cosgrave

Experts in our system

1
Leonie S Young
Royal College of Surgeons in Ireland
Total Publications: 42
 
2
Arnold D K Hill
Royal College of Surgeons in Ireland
Total Publications: 110