Cited by 39TGF-β signaling in diseasesHER2/EGFR in Cancer ResearchLiver physiology and pathology

Quantitation of TGF-β proteins in mouse tissues shows reciprocal changes in TGF-β1 and TGF-β3 in normal vs neoplastic mammary epithelium

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Flanders, Kathleen C., Yang, Yu-an, Herrmann, Michelle, Chen, JinQiu, Mendoza, Nerissa, Mirza, Amer M., Wakefield, Lalage M.·2016·Oncotarget

Abstract

// Kathleen C. Flanders 1, * , Yu-an Yang 1, * , Michelle Herrmann 1 , JinQiu Chen 1 , Nerissa Mendoza 2 , Amer M. Mirza 2 , Lalage M. Wakefield 1 1 Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America 2 XOMA Corporation, Berkeley, California, United States of America * These authors have contributed equally to this work Correspondence to: Kathleen C. Flanders, e-mail: flanderk@mail.nih.gov Keywords: TGF-β isoforms, protein, quantitation, mouse tissues, mammary gland Received: October 28, 2015 Accepted: April 26, 2016 Published: May 17, 2016 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.

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Authors
Flanders, K. C., Yang, Y.-A., Herrmann, M., Chen, J., Mendoza, N., Mirza, A. M., & Wakefield, L. M.
Affiliations
  • National Institutes of Health (US)
  • Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America
  • XOMA (United States) (US)
Corresponding author
  • Flanders, Kathleen C.
  • Yang, Yu-an
Venue
Oncotarget
Published
2016-05-17
Volume
7
Issue
25
Pages
38164-38179
ISSN
1949-2553 (ISSN-L)
OpenAlex
W2404501987
Cited by
39
References
65
Citations by year
2026: 4 · 2025: 4 · 2024: 11 · 2023: 9 · 2022: 2 · 2021: 5 · 2020: 2 · 2019: 1 · 2018: 1
FWCI
0.35
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Oncotarget (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Cancer Institute (ZIABC010881)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
  • Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords
TGF-beta isoforms, TGF-β1, TGF-beta2, TGF-beta3, mammary gland, mammary carcinogenesis, mammary epithelium, protein quantification, tissue-specific gene expression, mouse strains, luminal epithelium
MeSH terms
Animals, Female, Humans, Mammary Neoplasms, Experimental, Mice, Inbred BALB C, Transforming Growth Factor beta, Protein Isoforms, Mice, Transforming Growth Factor beta1, Transforming Growth Factor beta3

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