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Article: Sex hormone-induced mammary carcinogenesis in female Noble rats: The role of androgens

TitleSex hormone-induced mammary carcinogenesis in female Noble rats: The role of androgens
Authors
Issue Date1999
PublisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
Citation
Carcinogenesis, 1999, v. 20 n. 8, p. 1597-1606 How to Cite?
AbstractBreast cancer is the most common cancer and the second most frequent cause of cancer death in women. Despite extensive research, the precise mechanisms of breast carcinogenesis remain unclear. We have shown that in female rats, treatment with a combination of oestrogen and testosterone can induce a high incidence of mammary cancer. The dosage of testosterone affects only the latency period of mammary cancer, not the final incidence. Based on these observations, we hypothesize that oestrogen and androgens may act in concert on the mammary gland to induce mammary carcinogenesis, with oestrogen serving as the predominant initiator whereas the androgen acts as a major promoter. In the present study, we report the changes in morphology of the mammary gland with special emphasis on the perialveolar or interlobular stroma after treatment with various sex hormone protocols. Our data showed that after treatment with testosterone, either alone or in combination with 17β-oestradiol, there was overexpression of the androgen receptor in alveolar or ductal epithelial cells. Concurrent with strong expression of the androgen receptor in epithelium, there was also an increase in the amount of perialveolar and interlobular connective tissue, a decrease in surrounding adipose tissue and an increase in proliferation rate of fibroblast-like cells in the stroma. All these changes were blocked by simultaneous implantation of flutamide, indicating that androgens play a crucial role in the process despite the absence of androgen receptors in stromal cells. We further measured the mammary gland density (MGD), in order to determine the ratio of fatty to non-fatty tissue. The data showed that MGD values were significantly higher in animals treated with testosterone alone or in combination with 17β-oestradiol than in those treated with 17β-oestradiol alone or in controls. Furthermore, treatment with different doses of testosterone resulted in an increase in MGD in a dose-dependent manner. These findings highlight the effect of androgens on the stroma, probably through a paracrine action of epithelial cells. The stroma may, in turn, promote mammary carcinogenesis in a reciprocal fashion.
Persistent Identifierhttp://hdl.handle.net/10722/67498
ISSN
2015 Impact Factor: 4.874
2015 SCImago Journal Rankings: 2.439
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorXie, Ben_HK
dc.contributor.authorTsao, SWen_HK
dc.contributor.authorWong, YCen_HK
dc.date.accessioned2010-09-06T05:55:40Z-
dc.date.available2010-09-06T05:55:40Z-
dc.date.issued1999en_HK
dc.identifier.citationCarcinogenesis, 1999, v. 20 n. 8, p. 1597-1606en_HK
dc.identifier.issn0143-3334en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67498-
dc.description.abstractBreast cancer is the most common cancer and the second most frequent cause of cancer death in women. Despite extensive research, the precise mechanisms of breast carcinogenesis remain unclear. We have shown that in female rats, treatment with a combination of oestrogen and testosterone can induce a high incidence of mammary cancer. The dosage of testosterone affects only the latency period of mammary cancer, not the final incidence. Based on these observations, we hypothesize that oestrogen and androgens may act in concert on the mammary gland to induce mammary carcinogenesis, with oestrogen serving as the predominant initiator whereas the androgen acts as a major promoter. In the present study, we report the changes in morphology of the mammary gland with special emphasis on the perialveolar or interlobular stroma after treatment with various sex hormone protocols. Our data showed that after treatment with testosterone, either alone or in combination with 17β-oestradiol, there was overexpression of the androgen receptor in alveolar or ductal epithelial cells. Concurrent with strong expression of the androgen receptor in epithelium, there was also an increase in the amount of perialveolar and interlobular connective tissue, a decrease in surrounding adipose tissue and an increase in proliferation rate of fibroblast-like cells in the stroma. All these changes were blocked by simultaneous implantation of flutamide, indicating that androgens play a crucial role in the process despite the absence of androgen receptors in stromal cells. We further measured the mammary gland density (MGD), in order to determine the ratio of fatty to non-fatty tissue. The data showed that MGD values were significantly higher in animals treated with testosterone alone or in combination with 17β-oestradiol than in those treated with 17β-oestradiol alone or in controls. Furthermore, treatment with different doses of testosterone resulted in an increase in MGD in a dose-dependent manner. These findings highlight the effect of androgens on the stroma, probably through a paracrine action of epithelial cells. The stroma may, in turn, promote mammary carcinogenesis in a reciprocal fashion.en_HK
dc.languageengen_HK
dc.publisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/en_HK
dc.relation.ispartofCarcinogenesisen_HK
dc.rightsCarcinogenesis. Copyright © Oxford University Press.en_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshEstradiol - adverse effectsen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshKi-67 Antigen - analysisen_HK
dc.subject.meshMammary Glands, Animal - chemistry - drug effects - pathologyen_HK
dc.subject.meshMammary Neoplasms, Experimental - chemically induced - chemistry - pathologyen_HK
dc.subject.meshNeoplasms, Hormone-Dependent - chemically induceden_HK
dc.subject.meshRatsen_HK
dc.subject.meshRats, Inbred Strainsen_HK
dc.subject.meshReceptors, Androgen - analysisen_HK
dc.subject.meshReceptors, Estrogen - analysisen_HK
dc.subject.meshTestosterone - adverse effectsen_HK
dc.titleSex hormone-induced mammary carcinogenesis in female Noble rats: The role of androgensen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0143-3334&volume= 20 No8&spage=1597&epage=1606&date=1999&atitle=Sex+hormone-induced+mammary+carcinogenesis+in+female+Noble+rats:+the+role+of+androgensen_HK
dc.identifier.emailTsao, SW:gswtsao@hkucc.hku.hken_HK
dc.identifier.emailWong, YC:ycwong@hkucc.hku.hken_HK
dc.identifier.authorityTsao, SW=rp00399en_HK
dc.identifier.authorityWong, YC=rp00316en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1093/carcin/20.8.1597en_HK
dc.identifier.pmid10426813-
dc.identifier.scopuseid_2-s2.0-0032841099en_HK
dc.identifier.hkuros47661en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0032841099&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume20en_HK
dc.identifier.issue8en_HK
dc.identifier.spage1597en_HK
dc.identifier.epage1606en_HK
dc.identifier.isiWOS:000082004100032-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridXie, B=7201872727en_HK
dc.identifier.scopusauthoridTsao, SW=7102813116en_HK
dc.identifier.scopusauthoridWong, YC=7403041798en_HK

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