Growth Inhibition of Breast Cancer Cells by Interferons

Institution: University of California, Los Angeles
Investigator(s): Ke Shuai, Ph.D. -
Award Cycle: 1995 (Cycle I) Grant #: 1KB-0224 Award: $225,000
Award Type: New Investigator Awards
Research Priorities
Detection, Prognosis and Treatment>Innovative Treatment Modalities: search for a cure



Initial Award Abstract (1995)
Interferons (IFNs) have antiproliferative actions and can inhibit the growth of many tumor cells including breast cancer cells. Unfortunately, clinical trials using IFN as a single drug for breast cancer have not been satisfactory due to a wide range of side effects resulting from the usage of high doses of IFNs. However, it has been shown that the strategy to use tamoxifen in combination with IFN can greatly enhance the effects of tamoxifen on breast cancer. Based on our most current understanding of the molecular basis of IFN action, we have recently discovered a protein molecule which can greatly enhance the antiproliferative effects of IFNs. The overall goal of this project is to study the effects of this protein molecule on the growth inhibition of breast cancer cells. We will also test our hypothesis that this protein molecule can greatly enhance the antigrowth effects of tamoxifen on breast cancer cells. This research will lead to the design of rational preventative strategies for breast cancer employing IFNs.

To study the effects of this molecule on the growth inhibition of breast cancer cells, we will first introduce this protein into breast cancer cells using a system in which we can control the level of this protein. We will then analyze the growth of breast cancer cells in the presence of different levels of this protein molecule. The optimal concentrations of IFNs for growth inhibition of breast cancer cells in the presence of this protein will also be determined. Next, we will investigate the possibility that this protein molecule can greatly enhance the anti-proliferative effects of tamoxifen on breast cancer cells. The growth inhibition of breast cancer cells by tamoxifen in the presence or absence of this protein molecule will be determined and analyzed. We will also determine the potential effects of this protein molecule on the level of estrogen receptor by Northern blot and Western blot analysis.


Final Report (1998)
Interferon (IFN), produced by cells in the body, has powerful anti-tumor activity. A protein inside of cells, named Stat1, plays an important role in IFN action. The overall goal of this research is to study the growth inhibition of breast cancer cells by IFN. Our approach has been to introduce normal and mutant forms of StatI into breast cancer cells to study its function.

We have tested the effect of mStat1, a hyperactive form of the Stat1 protein. In fibroblasts mStat1 will enhance the antiproliferative activity of IFN. However, in breast cancer cells it was found that mStat1 failed to enhance the antigrowth activity of IFN. Thus, we began to look for and additional mechanism that could protect breast cancer cells from the antigrowth activity of IFNs. First, we found that a protein factor named NF-kB was activated by IFN in breast cancer cells. And, NF-kB has been shown to protect tumor cells from death induced by other antiproliferative signals. However, NF-kB had no effect on the IFN-induced antiproliferative activity. Finally, we were successful in showing that two other signaling proteins inside of breast cancer cells, SOCS suppressor of cytokine signaling)-1 and SOCS-3, were able to block the IFN-induced antiproliferative activity.

These results may enhance our ability to design rational therapeutic strategy for the treatment and prevention of breast cancer.

The suppressor of cytokine signaling (SOCS) 1 and SOCS3 but not SOCS2 proteins inhibit interferon-mediated antiviral and antiproliferative activities
Periodical:Journal of Biological Chemistry
Index Medicus: J Biol Chem
Authors: Song, M.M., Shuai, K
Yr: 1998 Vol: 273 Nbr: Abs: Pg:35056-62