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Article: Sex hormone-induced mammary carcinogenesis in female Noble rats: Expression of TGF-β1 and its receptors, TGF-α, and EGF-R in mammary carcinogenesis

TitleSex hormone-induced mammary carcinogenesis in female Noble rats: Expression of TGF-β1 and its receptors, TGF-α, and EGF-R in mammary carcinogenesis
Authors
Issue Date1999
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, 1999, v. 58 n. 3, p. 227-239 How to Cite?
AbstractWe have established a Noble rat model to explore the mechanisms of hormonal mammary carcinogenesis, in which the role of androgen in promoting mammary carcinogenesis was highlighted. We have also established that stromal-epithelial interactions may be responsible for the promotional effects of testosterone in mammary carcinogenesis. Based on these understandings, in the present study we examined the expression of transforming growth factor beta-1 (TGF-β1) and its receptors (TGF-β RI, TGF-β RII), transforming growth factor alpha (TGF-α), and epidermal growth factor receptor (EGF-R) in 'pre-malignant' mammary glands treated with different protocols of sex hormones, as well as in mammary cancers. We observed that TGF-β1 was strongly expressed in most mammary tumors, whereas TGF-β RI and TGF-β RII were negative in most mammary tumor cells. The results from comparative study of 'pre-malignant' glands further showed that when the animals were treated with testosterone, either alone or in combination with 17β-estradiol, the mammary gland epithelial cells expressed high levels of TGF-β1. This over-expression of TGF-β1 can be blocked by flutamide, indicating that testosterone may be responsible for the expression of TGF-β1 in mammary glands. TGF-β RI and TGF-β RII were also expressed strongly in testosterone-treated mammary epithelial cells and only weakly detectable in 17β-estradiol treated and control mammary epithelial cells. Furthermore, TGF-β RI and TGF-β RII were also expressed in stromal cells, both in mammary tumors and in hormone-treated mammary glands. These observations indicate that the mechanism of testosterone in mammary carcinogenesis may be through its regulation of expression of TGF-β1 and its receptors. On the other hand, TGF-α was also expressed in all 39 mammary cancers, while only 81% of the cancers were EGF-R positive. TGF-α was also strongly expressed in stromal cells in all three experimental groups, but only moderately expressed in epithelial cells when treated with a combination of testosterone and 17β-estradiol. By contrast, EGF-R was strongly expressed in epithelial cells in the three experimental groups but negative in stromal cells. Flutamide or tamoxifen was unable to block the expression of TGF-α induced by the combined sex hormone treatment. However, they were effective in blocking the expression of TGF-α when the animals were treated with testosterone or 17β-estradiol alone, respectively. These results suggest that both testosterone and 17β-estradiol may be required for the over-expression of TGF-α in the mammary carcinogenesis induced by sex hormones. To our knowledge, this is the first experimental study to explore the regulation of TGF-β1, TGF-α, and their receptors by testosterone and 17β-estradiol in mammary carcinogenesis.
Persistent Identifierhttp://hdl.handle.net/10722/149581
ISSN
2015 Impact Factor: 4.085
2015 SCImago Journal Rankings: 2.424
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorXie, Ben_US
dc.contributor.authorTsao, SWen_US
dc.contributor.authorWong, YCen_US
dc.date.accessioned2012-06-26T05:55:33Z-
dc.date.available2012-06-26T05:55:33Z-
dc.date.issued1999en_US
dc.identifier.citationBreast Cancer Research And Treatment, 1999, v. 58 n. 3, p. 227-239en_US
dc.identifier.issn0167-6806en_US
dc.identifier.urihttp://hdl.handle.net/10722/149581-
dc.description.abstractWe have established a Noble rat model to explore the mechanisms of hormonal mammary carcinogenesis, in which the role of androgen in promoting mammary carcinogenesis was highlighted. We have also established that stromal-epithelial interactions may be responsible for the promotional effects of testosterone in mammary carcinogenesis. Based on these understandings, in the present study we examined the expression of transforming growth factor beta-1 (TGF-β1) and its receptors (TGF-β RI, TGF-β RII), transforming growth factor alpha (TGF-α), and epidermal growth factor receptor (EGF-R) in 'pre-malignant' mammary glands treated with different protocols of sex hormones, as well as in mammary cancers. We observed that TGF-β1 was strongly expressed in most mammary tumors, whereas TGF-β RI and TGF-β RII were negative in most mammary tumor cells. The results from comparative study of 'pre-malignant' glands further showed that when the animals were treated with testosterone, either alone or in combination with 17β-estradiol, the mammary gland epithelial cells expressed high levels of TGF-β1. This over-expression of TGF-β1 can be blocked by flutamide, indicating that testosterone may be responsible for the expression of TGF-β1 in mammary glands. TGF-β RI and TGF-β RII were also expressed strongly in testosterone-treated mammary epithelial cells and only weakly detectable in 17β-estradiol treated and control mammary epithelial cells. Furthermore, TGF-β RI and TGF-β RII were also expressed in stromal cells, both in mammary tumors and in hormone-treated mammary glands. These observations indicate that the mechanism of testosterone in mammary carcinogenesis may be through its regulation of expression of TGF-β1 and its receptors. On the other hand, TGF-α was also expressed in all 39 mammary cancers, while only 81% of the cancers were EGF-R positive. TGF-α was also strongly expressed in stromal cells in all three experimental groups, but only moderately expressed in epithelial cells when treated with a combination of testosterone and 17β-estradiol. By contrast, EGF-R was strongly expressed in epithelial cells in the three experimental groups but negative in stromal cells. Flutamide or tamoxifen was unable to block the expression of TGF-α induced by the combined sex hormone treatment. However, they were effective in blocking the expression of TGF-α when the animals were treated with testosterone or 17β-estradiol alone, respectively. These results suggest that both testosterone and 17β-estradiol may be required for the over-expression of TGF-α in the mammary carcinogenesis induced by sex hormones. To our knowledge, this is the first experimental study to explore the regulation of TGF-β1, TGF-α, and their receptors by testosterone and 17β-estradiol in mammary carcinogenesis.en_US
dc.languageengen_US
dc.publisherSpringer New York LLC. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=0167-6806en_US
dc.relation.ispartofBreast Cancer Research and Treatmenten_US
dc.subject.meshAnimalsen_US
dc.subject.meshCell Transformation, Neoplasticen_US
dc.subject.meshEpithelial Cells - Drug Effects - Physiologyen_US
dc.subject.meshEstradiol - Pharmacologyen_US
dc.subject.meshFemaleen_US
dc.subject.meshMammary Glands, Animal - Pathology - Physiologyen_US
dc.subject.meshMammary Neoplasms, Animal - Metabolism - Pathologyen_US
dc.subject.meshRatsen_US
dc.subject.meshReceptor, Epidermal Growth Factor - Biosynthesisen_US
dc.subject.meshTestosterone - Pharmacologyen_US
dc.subject.meshTransforming Growth Factor Alpha - Biosynthesisen_US
dc.subject.meshTransforming Growth Factor Beta - Biosynthesisen_US
dc.titleSex hormone-induced mammary carcinogenesis in female Noble rats: Expression of TGF-β1 and its receptors, TGF-α, and EGF-R in mammary carcinogenesisen_US
dc.typeArticleen_US
dc.identifier.emailTsao, SW:gswtsao@hkucc.hku.hken_US
dc.identifier.emailWong, YC:ycwong@hkucc.hku.hken_US
dc.identifier.authorityTsao, SW=rp00399en_US
dc.identifier.authorityWong, YC=rp00316en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1023/A:1006349532643-
dc.identifier.pmid10718485-
dc.identifier.scopuseid_2-s2.0-0033491957en_US
dc.identifier.hkuros48135-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0033491957&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume58en_US
dc.identifier.issue3en_US
dc.identifier.spage227en_US
dc.identifier.epage239en_US
dc.identifier.isiWOS:000085009700005-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridXie, B=7201872727en_US
dc.identifier.scopusauthoridTsao, SW=7102813116en_US
dc.identifier.scopusauthoridWong, YC=7403041798en_US

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