Document Detail

The role of TGF-beta production in growth inhibition of breast-tumor cells by progestins.
MedLine Citation:
PMID:  7705937     Owner:  NLM     Status:  MEDLINE    
We have studied the influence of synthetic progestins on the estrogen-induced proliferation and type-beta transforming-growth-factor (TGF-beta) production of 3 breast-tumor cell lines. In long-term growth experiments, progestins inhibited proliferation of T47D cells, while a specific T47D variant and MCF7 cells were not affected, despite the presence of functional progesterone receptors. The effect of progestins was biphasic, since an initial stimulation of proliferation was followed by a prolonged inhibition. This response suggests the involvement of a progestin-induced negative growth regulator. We show here that TGF-beta s do not fulfill this role since (i) the progestin-induced T47D cells are not sensitive to TGF-beta 1, -beta 2 or -beta 3, (ii) secretion of TGF-beta s is decreased by progestins in all 3 cell lines, and (iii) TGF-beta neutralizing antibodies do not reverse progestin-induced growth inhibition. Furthermore, evidence was obtained that medium conditioned by T47D cells does not contain any other growth inhibitor to which this cell line responds in a negative autocrine manner. In contrast, MCF7 cells are growth-inhibited by all 3 TGF-beta isoforms, but are not growth-inhibited by progestins, suggesting that there is no correlation between growth inhibition by progestins and responsiveness to and production of TGF-beta in vitro. Although TGF-beta is a strong growth inhibitor of normal mammary tissue, recent evidence suggests that, in malignant tissue, enhanced TGF-beta secretion correlates with increased malignancy. Therefore, a progestin-induced decrease in TGF-beta production, as observed here, may lead to enhanced proliferation of normal but not malignant mammary epithelium.
E Kalkhoven; L Kwakkenbos-Isbrücker; C L Mummery; S W de Laat; A J van den Eijnden-van Raaij; P T van der Saag; B van der Burg
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  61     ISSN:  0020-7136     ISO Abbreviation:  Int. J. Cancer     Publication Date:  1995 Mar 
Date Detail:
Created Date:  1995-05-09     Completed Date:  1995-05-09     Revised Date:  2007-07-24    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  80-6     Citation Subset:  IM    
Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht.
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MeSH Terms
Breast Neoplasms / drug therapy*,  metabolism*,  pathology
Cell Division / drug effects
Estradiol Antagonists / pharmacology
Progesterone Congeners / pharmacology*
Transforming Growth Factor beta / biosynthesis*,  secretion
Tumor Cells, Cultured
Reg. No./Substance:
0/Estradiol Antagonists; 0/Progesterone Congeners; 0/Transforming Growth Factor beta

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