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

被引：23

作者：

Flanders, Kathleen C. ^{[1
]}

Yang, Yu-an ^{[1
]}

Herrmann, Michelle ^{[1
]}

Chen, JinQiu ^{[1
]}

Mendoza, Nerissa ^{[2
]}

Mirza, Amer M. ^{[2
]}

Wakefield, Lalage M. ^{[1
]}

机构：

[1] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA

[2] Xoma Corp, Berkeley, CA 94710 USA

来源：

ONCOTARGET | 2016年 / 7卷 / 25期

关键词：

TGF-beta isoforms; protein; quantitation; mouse tissues; mammary gland; TRANSFORMING-GROWTH-FACTOR; INDUCED PULMONARY-FIBROSIS; BREAST-CANCER; IMMUNOHISTOCHEMICAL LOCALIZATION; GROWTH-FACTOR-BETA-1; GENE; EXPRESSION PATTERNS; TRANSGENIC MICE; MESSENGER-RNA; TUMOR; DISEASE;

D O I：

10.18632/oncotarget.9416

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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

引用

页码：38164 / 38179

页数：16

共 66 条

[1] AN ASSAY FOR TRANSFORMING GROWTH-FACTOR-BETA USING CELLS TRANSFECTED WITH A PLASMINOGEN-ACTIVATOR INHIBITOR-1 PROMOTER LUCIFERASE CONSTRUCT [J].

ABE, M ;

HARPEL, JG ;

METZ, CN ;

NUNES, I ;

LOSKUTOFF, DJ ;

RIFKIN, DB .

ANALYTICAL BIOCHEMISTRY, 1994, 216 (02) :276-284

[2]

Akhurst RJ, 2001, TRENDS CELL BIOL, V11, pS44, DOI 10.1016/S0962-8924(01)82259-5

[3] Targeting the TGFβ signalling pathway in disease [J].

Akhurst, Rosemary J. ;

Hata, Akiko .

NATURE REVIEWS DRUG DISCOVERY, 2012, 11 (10) :790-811

[4]

Alonso DF, 1996, J SURG ONCOL, V62, P288, DOI 10.1002/(SICI)1096-9098(199608)62:4<288::AID-JSO14>3.0.CO

[5]

2-1

[6] Transforming growth factor beta-1 in rectal tumour, mucosa and plasma in relation to radiotherapy and clinical outcome in rectal cancer patients [J].

Angenete, Eva ;

Langenskiold, Marcus ;

Palmgren, Ingrid ;

Falk, Peter ;

Oresland, Tom ;

Ivarsson, Marie-Louise .

INTERNATIONAL JOURNAL OF COLORECTAL DISEASE, 2007, 22 (11) :1331-1338

[7] INHIBITION OF TRANSLATION OF TRANSFORMING GROWTH FACTOR-BETA-3 MESSENGER-RNA BY ITS 5' UNTRANSLATED REGION [J].

ARRICK, BA ;

LEE, AL ;

GRENDELL, RL ;

DERYNCK, R .

MOLECULAR AND CELLULAR BIOLOGY, 1991, 11 (09) :4306-4313

[8]

ASLAKSON CJ, 1992, CANCER RES, V52, P1399

[9]

ASSOIAN RK, 1983, J BIOL CHEM, V258, P7155

[10]

BARCELLOSHOFF MH, 1995, AM J PATHOL, V147, P1228

← 1 2 3 4 5 6 7 →