Quantitation of TGF-? proteins in mouse tissues shows reciprocal changes in TGF-?1 and TGF-?3 in normal vs neoplastic mammary epithelium.

ABSTRACT: Transforming growth factor-?s (TGF-?s) regulate tissue homeostasis, and their expression is perturbed in many diseases. The three isoforms (TGF-?1, -?2, and -?3) have similar bioactivities in vitro but show distinct activities in vivo. Little quantitative information exists for expression of TGF-? isoform proteins in physiology or disease. We developed an optimized method to quantitate protein levels of the three isoforms, using a Luminex® xMAP®-based multianalyte assay following acid-ethanol extraction of tissues. Analysis of multiple tissues and plasma from four strains of adult mice showed that TGF-?1 is the predominant isoform with TGF-?2 being ~10-fold lower. There were no sex-specific differences in isoform expression, but some tissues showed inter-strain variation, particularly for TGF-?2. The only adult tissue expressing appreciable TGF-?3 was the mammary gland, where its levels were comparable to TGF-?1. In situ hybridization showed the luminal epithelium as the major source of all TGF-? isoforms in the normal mammary gland. TGF-?1 protein was 3-8-fold higher in three murine mammary tumor models than in normal mammary gland, while TGF-?3 protein was 2-3-fold lower in tumors than normal tissue, suggesting reciprocal regulation of these isoforms in mammary tumorigenesis.

SUBMITTER: Flanders KC 

PROVIDER: S-EPMC5122380 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature