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Article: The effect of flutamide and tamoxifen on sex hormone-induced mammary carcinogenesis and pituitary adenoma

TitleThe effect of flutamide and tamoxifen on sex hormone-induced mammary carcinogenesis and pituitary adenoma
Authors
KeywordsFlutamide
Mammary carcinogenesis
Pituitary adenoma
Sex hormones
Tamoxifen
Issue Date2002
PublisherSpringer New York LLC. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=0167-6806
Citation
Breast Cancer Research And Treatment, 2002, v. 72 n. 2, p. 153-162 How to Cite?
AbstractWe have established a female Noble rat model to explore the mechanisms of hormonal mammary carcinogenesis. Based on the previous finding that the dose of testosterone affects only the latency period of mammary cancer, not the final incidence and that androgen upregulates apoptotic activity in pre-malignant mammary glands, we hypothesised that estrogen is the initiator and androgen the promoter for hormonal mammary carcinogenesis of the rats. In the present study, rats were treated with the sex hormones together with flutamide and tamoxifen for both short term (7 and 13 weeks) and long term (12 months) durations. We showed that tamoxifen could totally inhibit mammary carcinogenesis while flutamide cause a delay and reduction in tumour incidence in the 12 months treatment term. Blocking effect of flutamide and tamoxifen on T + E2 (testosterone and 17β-estradiol) short-terms treatment was demonstrated by the similar histological changes identified in the mammary glands of the T + E2 and drug treated rats to that of the age matched E2 and T controls, respectively. These findings give further support for the role of estrogen and androgen in mammary carcinogenesis. Autopsy of the tumour bearing rats showed presence of pituitary macroadenoma causing compression and atrophy of the brain stem. Immunohistochemical staining of these adenomas showed a predominance of prolactin-secreting cells. Serum assay also showed a corresponding increase in circulatory prolactin level. Tamoxifen was also effective in blocking the formation of pituitary adenoma in the sex hormone treated rats. Pituitary size and level of prolactin were higher in the T + E2 + flutamide group than the T + E2 group in both short-term and long-term treatments. It suggests that testosterone may have a role in counteracting estradiol stimulation on the pituitary lactotropes although it is synergistic to estrogen in mammary carcinogenesis. Pituitary adenomas were found in all rats that developed mammary adenocarcinoma but not vice versa suggesting that prolactin level elevation alone cannot lead to mammary tumorigenesis. The animal model, in addition to mammary carcinogenesis, may be useful for investigation of anti-estrogen therapy in pituitary adenomas.
Persistent Identifierhttp://hdl.handle.net/10722/67822
ISSN
2015 Impact Factor: 4.085
2015 SCImago Journal Rankings: 2.424
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLeung, Gen_HK
dc.contributor.authorTsao, SWen_HK
dc.contributor.authorWong, YCen_HK
dc.date.accessioned2010-09-06T05:58:34Z-
dc.date.available2010-09-06T05:58:34Z-
dc.date.issued2002en_HK
dc.identifier.citationBreast Cancer Research And Treatment, 2002, v. 72 n. 2, p. 153-162en_HK
dc.identifier.issn0167-6806en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67822-
dc.description.abstractWe have established a female Noble rat model to explore the mechanisms of hormonal mammary carcinogenesis. Based on the previous finding that the dose of testosterone affects only the latency period of mammary cancer, not the final incidence and that androgen upregulates apoptotic activity in pre-malignant mammary glands, we hypothesised that estrogen is the initiator and androgen the promoter for hormonal mammary carcinogenesis of the rats. In the present study, rats were treated with the sex hormones together with flutamide and tamoxifen for both short term (7 and 13 weeks) and long term (12 months) durations. We showed that tamoxifen could totally inhibit mammary carcinogenesis while flutamide cause a delay and reduction in tumour incidence in the 12 months treatment term. Blocking effect of flutamide and tamoxifen on T + E2 (testosterone and 17β-estradiol) short-terms treatment was demonstrated by the similar histological changes identified in the mammary glands of the T + E2 and drug treated rats to that of the age matched E2 and T controls, respectively. These findings give further support for the role of estrogen and androgen in mammary carcinogenesis. Autopsy of the tumour bearing rats showed presence of pituitary macroadenoma causing compression and atrophy of the brain stem. Immunohistochemical staining of these adenomas showed a predominance of prolactin-secreting cells. Serum assay also showed a corresponding increase in circulatory prolactin level. Tamoxifen was also effective in blocking the formation of pituitary adenoma in the sex hormone treated rats. Pituitary size and level of prolactin were higher in the T + E2 + flutamide group than the T + E2 group in both short-term and long-term treatments. It suggests that testosterone may have a role in counteracting estradiol stimulation on the pituitary lactotropes although it is synergistic to estrogen in mammary carcinogenesis. Pituitary adenomas were found in all rats that developed mammary adenocarcinoma but not vice versa suggesting that prolactin level elevation alone cannot lead to mammary tumorigenesis. The animal model, in addition to mammary carcinogenesis, may be useful for investigation of anti-estrogen therapy in pituitary adenomas.en_HK
dc.languageengen_HK
dc.publisherSpringer New York LLC. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=0167-6806en_HK
dc.relation.ispartofBreast Cancer Research and Treatmenten_HK
dc.subjectFlutamideen_HK
dc.subjectMammary carcinogenesisen_HK
dc.subjectPituitary adenomaen_HK
dc.subjectSex hormonesen_HK
dc.subjectTamoxifenen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshAnticarcinogenic Agents - pharmacologyen_HK
dc.subject.meshBreast - drug effectsen_HK
dc.subject.meshBreast Neoplasms - chemically induced - prevention & controlen_HK
dc.subject.meshCarcinogenicity Tests - methodsen_HK
dc.subject.meshEstradiol - pharmacologyen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshFlutamide - pharmacologyen_HK
dc.subject.meshGonadal Steroid Hormones - pharmacologyen_HK
dc.subject.meshPituitary Gland - drug effectsen_HK
dc.subject.meshProlactinoma - chemically induced - prevention & controlen_HK
dc.subject.meshRatsen_HK
dc.subject.meshTamoxifen - pharmacologyen_HK
dc.subject.meshTestosterone - pharmacologyen_HK
dc.titleThe effect of flutamide and tamoxifen on sex hormone-induced mammary carcinogenesis and pituitary adenomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0167-6806&volume=72&spage=153&epage=162&date=2002&atitle=The+effect+of+flutamide+and+tamoxifen+on+sex+hormone-induced+mammary+carcinogenesis+and+pituitary+adenomaen_HK
dc.identifier.emailLeung, G:gmleung@hku.hken_HK
dc.identifier.emailTsao, SW:gswtsao@hkucc.hku.hken_HK
dc.identifier.emailWong, YC:ycwong@hkucc.hku.hken_HK
dc.identifier.authorityLeung, G=rp00460en_HK
dc.identifier.authorityTsao, SW=rp00399en_HK
dc.identifier.authorityWong, YC=rp00316en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1023/A:1014864231689en_HK
dc.identifier.pmid12038706-
dc.identifier.scopuseid_2-s2.0-0036115888en_HK
dc.identifier.hkuros65826en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0036115888&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume72en_HK
dc.identifier.issue2en_HK
dc.identifier.spage153en_HK
dc.identifier.epage162en_HK
dc.identifier.isiWOS:000174634400007-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLeung, G=7007159841en_HK
dc.identifier.scopusauthoridTsao, SW=7102813116en_HK
dc.identifier.scopusauthoridWong, YC=7403041798en_HK

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