TIEG: A Novel TGFß-Estrogen Regulated Early Gene Expressed in Osteoblasts, Breast Tissues and Other Cell and Tissue Types

Reference #:

1995-072

Inventors/Contributors

Thomas C. Spelsberg, Ph.D., Malayannan Subramaniam, Ph.D.

Description

A marker for detecting breast cancer and implications for pancreatic cancer. The novel TGFß/estrogen inducible gene (TIEG) has been identified in normal human fetal osteoblasts using differential-display PCR. TIEG is regulated by TGFß and estrogen in breast tissue, osteoblasts and other cell and tissue types. Thus in addition to being an interesting target for gene discovery, TIEG is a useful marker of ligand activity. The TIEG cDNA has been cloned and polyclonal antibodies have been produced. TIEG over-expression inhibits cancer cell growth in hepatocarcinoma and pancreatic carcinoma in culture. TIEG over-expression in some of these cancer cell lines mimics TGFß action by inhibiting cell growth and inducing apoptosis. Accordingly, this gene is situated on Chromosome 8 near sites of other cancer genes. TIEG is expressed differentially during development and bears resemblence to the SP-1 transcription factor. Polyclonal antibodies proven to work in immunocytochemistry in 15 human tissues; a recombinant protein purified from bacteria and bacullovirus. TIEG knockout studies in mouse are in progress. Recent data show that TIEG mRNA and protein levels correlate with grade/stage of breast cancer, and may be useful for predicting metastic potential. Data also suggest that the TIEG protein may be used as a marker for pancreatic cancer. New information in this area is being accrued quickly, in part due to the wealth of tissue specimens and concomitant medical histories available at Mayo. This novel tumor suppressor gene, and protein product, are proving to be interesting as potential markers and prognostic indicators of cancer progression. Additionally, the projects currently underway, as well as the reagents developed to date would be important additions to any program related to gene discovery in the breast cancer, bone, hormone, cytokine and other cancer research areas.

Patent Status

	U.S. Patent Number 5,981,217 Issued November 09, 1999 U.S. Patent Number 6,207,375 Issued March 27, 2001