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. Transcriptional activation of c-myc is an early response to estrogen treatment and we have previously shown that induction of c-Myc quantitatively reproduces the effects of estrogen on cell cycle progression. Furthermore, c-Myc induction mimics other downstream effects of estrogen including activation of cyclin E-Cdk2 by decreased association with the CDK inhibitor p2l. Accumulating evidence suggests that the transforming capacity of c-Myc correlates more closely with transcriptional repression than with activation, raising the question of which function is the more important for c-Myc regulation of cell cycle progression. Our ongoing experimentation is thus aimed at using c-Myc mutants lacking specific functional domains to identify the domains that are important for estrogen-induced G(1) phase progression and the c-Myc target genes that mediate their effects. A panel of suitable constructs has now been generated and validated. These will be transfected into MCF-7 cells to assess their ability to recapitulate estrogen effects on parameters including cell cycle progression and cyclin E-Cdk2 activation. These experiments are expected to facilitate identification of the subset of c-Myc targets which are essential for estrogen-regulated proliferation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADA389563
Entities
People
- Eileen Rogan
Organizations
- Garvan Institute of Medical Research