Expression and secretion of TGF-beta isoforms and expression of TGF-beta-receptors I, II and III in normal and neoplastic human breast.
We investigated gene expression of the TGF-beta signalling system (including peptides and receptors) in normal and malignant breast tissue. Additionally, gene and protein expression was determined in a series of primary epithelial and stromal cultures derived from these tissues. TGF-beta isoforms and their receptors were expressed by both tissue sets, however the percentage of samples expressing each transcript varied. In normal breast, both TGF-beta1 and TGF-beta3 were found in most samples (88 and 89% respectively), with fewer expressing TGF-beta2 (68%). A similar pattern was evident in the tumours. Type I receptor of TGF-beta was constitutively expressed in normal breast and observed in most tumours (90%). Type II and III receptors of TGF-beta were expressed less frequently, although the type II receptor was mainly expressed by tumours (P=0. 0075). All primary cultures produced TGF-beta1 and TGF-beta2. Comparing respective cell populations, tumour stromal cells produced significantly more TGF-beta1 than those derived from normal breast (P<0.0001). Linear regression analysis showed stromal cultures derived from breast tumours exhibited a strong positive correlation (r=0.976) in the production of TGF-beta1 and TGF-beta2. Thus, TGF-beta and TGF-beta-receptors are widely and differentially expressed by normal and malignant breast and secretion of this peptide by epithelial and stromal cultures, in particular those derived from tumours, confirms its potential as an autocrine/paracrine regulator in breast cancer.
Chakravarthy
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D
Medical Research Laboratory, University of Hull, Hull HU6 7RX, UK.
Green
A R
AR
Green
V L
VL
Kerin
M J
MJ
Speirs
V
V
D030201:Activin Receptors, Type I; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism*; D018275:Carcinoma, Lobular / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D002478:Cells, Cultured / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D011509:Proteoglycans / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000378:metabolism
D009363:Neoplasm Proteins; D020033:Protein Isoforms; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; C071736:betaglycan; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II