The Influence of Stromal Transforming Growth Factor-Beta Receptor signaling on Mouse Mammary Neoplasia
Abstract
Our laboratory has developed transgenic mice that express a zinc-inducible, kinase-defective dominant-negative TGF-beta type II receptor in the mammary stroma (DNIIR). Recent evidence has accumulated implicating the stroma in regulating tumor formation. To determine if loss of TGF-beta signaling in the stroma affects tumor development transgenic and wild type mice were given pituitary isografts, zinc water and either left untreated or treated with 7, 12-dimethylbenz (a) anthracene (DMBA). Fifteen tumors developed in the wild type group on a full regiment (pituitary isograft, zinc and DMBA) while 16 tumors arose in the transgenic group with the same treatment. Both wild type and transgenic mice had an average of 1.5 tumors per mouse with an average latency of approximately 14 weeks. To identify genes regulated by TGF-beta in the mammary stroma a filter based array, commercial gene chip microarray and a custom mammary gland specific microarry were screened. Fifty-one genes have been analyzed by RT-PCR and 17 were confirmed for altered expression. The custom mammary gland specific microarry was verified and approximately 40% of the genes were found to be regulated 2 fold above or below the mean. Expression analysis of these genes is currently underway.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2003
- Accession Number
- ADA420069
Entities
People
- Michael R. Crowley
Organizations
- University of Alabama