MAPK-A Critical Intermediate in Anti-Estrogen Resistance
Abstract
Heregulin (HRG) is a growth factor that activates erbB-2-3-4 receptors. We have generated a novel model of tumor progression from a hormone-dependent to a hormone-independent phenotype by introducing HRG into breast cancer cells. We now would like to investigate the mechanism by which HRG induces tumor progression. Our working hypothesis is that expression of HRG induces an uncontrolled mitogen-activated protein kinase (MAPK) cascade producing unbalanced growth promoting genes. The proposed studies aim to determine whether blocking MAPK activation, cells revert to become hormone-dependent and antiestrogen responsive. During the first year of funding, we maintained the timeline outlined in the statement of work: a) Generated a Ras dominant negative (N17) regulated expression vector; b) Performed transfections into a number of MCF-71HRG cells and isolated specific drug-resistant clones; c) Partially characterized these clones; and d) Initiated the construction of the MAPK mutant. The major findings of our work are that expression of N17 in MCF-7HRG cells results in reversion from an anchorage-independent to anchorage-dependent phenotype. Moreover, when analyzing the response to estradiol, MCF-7/HRG/N17 cells regained hormonal response to a level of the wild type MCF-7 cells. This data demonstrates activation of the MAPK via the HRG pathway promotes an aggressive hormone-independent phenotype.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADA385905
Entities
People
- Ruth F. Lupu
Organizations
- University of California, Berkeley