Role of c-Myc in Estrogen Stimulated Cell Proliferation in Normal and Malignant Breast Epithelial Cells
Abstract
Estrogenic steroids have diverse physiological functions and are critically involved in the pathogenesis of breast cancer. The transcriptional regulator c-Myc has been implicated in estrogen-induced mitogenesis and we are therefore investigating the contribution of c-Myc to various downstream molecular and cellular events after estrogen stimulation. We have now developed a series of cell lines expressing c-Myc and mutants lacking one or both of the conserved 'Myc boxes' required for transcriptional regulation activity, under the control of an inducible promoter. Ongoing experiments are examining whether these mutants can mimic the effects of estrogen in activating cyclin E-Cdk2 and inducing cell cycle progression. We have recently shown that decreased expression of the CDK inhibitor p21, a c-Myc target, is critical for estrogen activation of cyclin E-Cdk2 and consequently the effect of the c-Myc mutants on p21 expression is of particular interest. We have also shown that decreased c-Myc expression can mimic the effects of antiestrogens. These data emphasise the importance of c-Myc regulation in estrogen and antiestrogen action.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA398172
Entities
People
- Eileen Rogen
Organizations
- Garvan Institute of Medical Research