title: Quantitation of TGF-β proteins in mouse tissues shows reciprocal changes in TGF-β1 and TGF-β3 in normal vs neoplastic mammary epithelium.
abstract: Transforming growth factor-βs (TGF-βs) regulate tissue homeostasis, and their expression is perturbed in many diseases. The three isoforms (TGF-β1, -β2, and -β3) have similar bioactivities in vitro but show distinct activities in vivo. Little quantitative information exists for expression of TGF-β 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-β1 is the predominant isoform with TGF-β2 being ~10-fold lower. There were no sex-specific differences in isoform expression, but some tissues showed inter-strain variation, particularly for TGF-β2. The only adult tissue expressing appreciable TGF-β3 was the mammary gland, where its levels were comparable to TGF-β1. In situ hybridization showed the luminal epithelium as the major source of all TGF-β isoforms in the normal mammary gland. TGF-β1 protein was 3-8-fold higher in three murine mammary tumor models than in normal mammary gland, while TGF-β3 protein was 2-3-fold lower in tumors than normal tissue, suggesting reciprocal regulation of these isoforms in mammary tumorigenesis.
authors.affiliation: Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Flanders
authors.affiliation: Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Yu-An
authors.initials: YA
authors.lastname: Yang
authors.affiliation: Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Michelle
authors.initials: M
authors.lastname: Herrmann
authors.affiliation: Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: JinQiu
authors.initials: J
authors.lastname: Chen
authors.affiliation: XOMA Corporation, Berkeley, California, United States of America.
authors.forename: Nerissa
authors.initials: N
authors.lastname: Mendoza
authors.affiliation: XOMA Corporation, Berkeley, California, United States of America.
authors.forename: Amer M
authors.initials: AM
authors.lastname: Mirza
authors.affiliation: Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Lalage M
authors.initials: LM
authors.lastname: Wakefield
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D020033:Protein Isoforms; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D053782:Transforming Growth Factor beta3 / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053782:Transforming Growth Factor beta3
keywords: TGF-β isoforms; mammary gland; mouse tissues; protein; quantitation