Cell Growth Arrest Mediated by STAT Proteins in Breast Cancer Cells
Abstract
We have previously demonstrated that EGF activated STAT1 in some cell lines, causing cell growth arrest and apoptosis. STAT3 is often activated together with STAT1 in response to EGF. It has recently been shown that STAT3 plays an crucial role in the cell cycle progression of BAF/BO3 pro-B cells. On the other hand, STAT3 activation by interleukin 6 has been demonstrated to prevent T-cells from apoptosis. More intriguingly, STAT3 but not STAT1 has been reported to be activated constitutively in several breast cancer cell lines and further enhanced in response to EGF. These recent findings led to a new hypothesis that STAT3 activated by EGF may stimulate the cell proliferation competing with activated STAT1, a negative regulator of the cell growth. Therefore, I decided to focus on STAT3 and disrupt its function in mice instead of mutating genome randomly with the frame shift mutagen. To achieve that, I employed the P1 phage-derived Cre/loxP site-specific recombination system since conventional STAT3 knockout mice had been shown to be embryonically lethal. Here I report on generation of mice carrying the loxP-flanked (floxed) (Stat3(sup F)) or -deleted (Stat3(-)) mutations in a germline configuration, which has been done.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADA376478
Entities
People
- Yoshiki Iwamoto
Organizations
- Yale University