HER-2 as a Progression Factor and Therapeutic Target in Breast Cancer.
Abstract
We studied the effect of down-regulation of HER-2 expression by ribozyme-targeting on in vitro and in vivo proliferation of cancer cells. HER-2 expression was found to be rate-limiting for the autocrine growth of some cell lines (SK-OV-3). Interestingly not only in HER-2 over expressing cancer cells but also in cells with low levels of expression (MCF-7) HER-2 appears to be the rate-limiting receptor to mediate the growth signals from EGF, and Heregulin-like ligands. These data demonstrate in human tumor cells that the HER-2 containing heterodimer is the rate-limiting signaling molecule, suggesting that the activity of HER-2 is due in part to its ability to increase the growth-response to stroma-derived EGF-like growth factors. Further we demonstrated that HER-2 required for the estradiol-mediated proliferative response of MCF-7 breast cancer cells through an indirect unknown mechanism. These data in conjunction with a recently published observation that HER-2 is involved in the interleukin-6 mediated proliferation of prostate carcinoma cells, demonstrate an increasing importance of this receptor in tumor biology. Finally, our data on the biological role of the truncated HER-2 receptor demonstrate that this protein can act as an intra cellularly expressed dominant negative receptor, which may protect cells from uncontrolled growth-factor mediated proliferation and progression to more aggressive tumors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 1998
- Accession Number
- ADA354367
Entities
People
- Frank Czubayko
Organizations
- Georgetown University