Document Detail

The role of androgens in mammary carcinogenesis.
MedLine Citation:
PMID:  11729946     Owner:  NLM     Status:  MEDLINE    
Despite extensive research, the precise mechanism of mammary carcinogenesis is unknown. We have developed an animal model in which a high incidence of mammary cancer can be induced within a period of several months using a combination of testosterone (T) and 17beta-estradiol (E2) without the addition of carcinogens. The induced mammary tumours mimic closely the human breast cancer in terms of histopathology. Our results showed that the two sex hormones work synergistically to induce a higher incidence of mammary cancer than either hormone treatment alone. The dosage of T affects only the latency period of mammary cancer but not the final incidence. The results further showed that treatment of T, either alone or in combination with E2, there was overexpression of the androgen receptor (AR) in alveolar or ductal epithelial cells but not in stromal cells. Together with overexpression of AR in epithelial cells, there was an increase in perialveolar and interlobular connective tissue as well as a decrease in surrounding adipose tissue, despite the absence of AR in stromal cells. There was also an increase in proliferation rate of fibroblast-like cells in stroma. These changes were blocked by implantation of flutamide, an antiandrogen, indicating that androgens play a crucial role in the process. These findings highlight that the effect of androgens on the stroma, may be through a paracrine action of epithelial cells. The changes in the stroma may, in turn, promote mammary carcinogeneis in a reciprocal manner.
Y C Wong; B Xie
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Italian journal of anatomy and embryology = Archivio italiano di anatomia ed embriologia     Volume:  106     ISSN:  1122-6714     ISO Abbreviation:  Ital J Anat Embryol     Publication Date:  2001  
Date Detail:
Created Date:  2001-12-03     Completed Date:  2002-04-30     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9612303     Medline TA:  Ital J Anat Embryol     Country:  Italy    
Other Details:
Languages:  eng     Pagination:  111-25     Citation Subset:  IM    
Department of Anatomy, Faculty of Medicine, The University of Hong Kong, HKSAR, China.
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MeSH Terms
Breast Neoplasms / etiology,  metabolism*,  pathology
Carcinoma / chemically induced,  metabolism*,  pathology
Cell Division / drug effects,  physiology
Disease Models, Animal
Disease Progression
Epithelial Cells / drug effects,  metabolism*,  pathology
Estradiol / blood,  metabolism*,  pharmacokinetics
Ki-67 Antigen / drug effects,  metabolism
Mammary Neoplasms, Experimental / chemically induced,  metabolism*,  pathology
Rats, Inbred Strains
Reaction Time / drug effects,  physiology
Receptors, Androgen / antagonists & inhibitors,  metabolism
Receptors, Estrogen / antagonists & inhibitors,  metabolism
Stromal Cells / drug effects,  metabolism*,  pathology
Testosterone / blood,  metabolism*,  pharmacokinetics
Reg. No./Substance:
0/Ki-67 Antigen; 0/Receptors, Androgen; 0/Receptors, Estrogen; 50-28-2/Estradiol; 58-22-0/Testosterone

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