MMP-8: A Breast Cancer Bone Metastasis Suppressor Gene
Annual rept. 22 Jul 2004-21 Jul 2005
UNIVERSITY OF MEDICINE AND DENTISTRY OF NEW JERSEY PISCATAWAY
Pagination or Media Count:
In order to study the role of MMP-8 on inhibition of cancer growth and progression, we initiated our work to clone the human MMP-8 cDNA and express it in vitro. The pcDNA3.1 contains the following elements human cytomegalovirus CMV immediate-early promoterenhancer that permits efficient, high-level expression of recombinant protein and V5 epitope that allows detection of recombinant protein with anti-V5 antibody. The MMP-8 cDNA with a V5-epitope tag was cloned downstream into the CMV promoter sequence. The construct pCMV-MMP-1-V5 was sequenced to verify cloning of the MMP-8 cDNA insert in frame. The molecular mechanisms of how TGF-beta1 mediates stimulation of invasion and formation of bone metastases have yet to be completely determined. In my laboratory, we have found that ATF-3 activating transcription factor- 3 is strongly stimulated and its level is sustained by TGF-beta1 in highly invasive and bone metastatic human breast cancer cells. A defect in repression of ATF-3 expression in breast cancer cells could lead to activation of genes that participate in multi-step breast cancer progression.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology