Normal breast tissue implanted into athymic nude mice identifies biomarkers of the effects of human pregnancy levels of estrogen.

2.50
Hdl Handle:
http://hdl.handle.net/10541/69778
Title:
Normal breast tissue implanted into athymic nude mice identifies biomarkers of the effects of human pregnancy levels of estrogen.
Authors:
Blance, Rognvald N; Sims, Andrew H; Anderson, Elizabeth; Howell, Anthony ( 0000-0002-3879-5991 ) ; Clarke, Robert B
Abstract:
We have generated a novel model system for the study of estrogen intervention in normal breast tissue. Nulliparous human breast tissue was implanted into immunocompromised nude mice and treated with high-dose estrogen to simulate the effects of pregnancy. Treatment of mice with human mid-pregnancy levels of 17beta-estradiol for a period of 4 weeks was followed by 4 weeks of withdrawal to mimic involution. Gene expression in the xenograft tissue was then analyzed by real-time reverse transcription-PCR to identify differences between treated and control tissues. Ten genes previously identified as altered by pregnancy in rodent models were found to be differentially expressed in human breast tissue with a > or =1.8-fold up-regulation of CDC42, TGFbeta3, DCN, KRT14, LTF, and AREG and a > or =0.7-fold down-regulation of STAT1, CTGF, IGF1, and VAMP1. Immunohistochemical analysis of archival paraffin-embedded adult premenopausal human breast tissue specimens identified a significantly lower level of expression of STAT1 (P < 0.05, Mann-Whitney U test) in parous compared with age-matched nulliparous tissue (median of 24% compared with 42% epithelial cells positive). We conclude that many of the pregnancy-induced breast cancer-protective changes observed in rodent models also occur in human breast tissue following intervention using human pregnancy levels of estrogen and that STAT1 expression is a potential biomarker of parity-induced breast cancer protection in the human breast.
Affiliation:
Breast Biology Group, School of Cancer and Imaging Sciences, Paterson Institute for Cancer Research, University of Manchester, Manchester, United Kingdom.
Citation:
Normal breast tissue implanted into athymic nude mice identifies biomarkers of the effects of human pregnancy levels of estrogen. 2009, 2 (3):257-64 Cancer Prev Res
Journal:
Cancer Prevention Research
Issue Date:
Mar-2009
URI:
http://hdl.handle.net/10541/69778
DOI:
10.1158/1940-6207.CAPR-08-0161
PubMed ID:
19258541
Type:
Article
Language:
en
ISSN:
1940-6215
Appears in Collections:
All Paterson Institute for Cancer Research; Medical Oncology; Breast Biology

Full metadata record

DC FieldValue Language
dc.contributor.authorBlance, Rognvald N-
dc.contributor.authorSims, Andrew H-
dc.contributor.authorAnderson, Elizabeth-
dc.contributor.authorHowell, Anthony-
dc.contributor.authorClarke, Robert B-
dc.date.accessioned2009-06-05T10:09:46Z-
dc.date.available2009-06-05T10:09:46Z-
dc.date.issued2009-03-
dc.identifier.citationNormal breast tissue implanted into athymic nude mice identifies biomarkers of the effects of human pregnancy levels of estrogen. 2009, 2 (3):257-64 Cancer Prev Resen
dc.identifier.issn1940-6215-
dc.identifier.pmid19258541-
dc.identifier.doi10.1158/1940-6207.CAPR-08-0161-
dc.identifier.urihttp://hdl.handle.net/10541/69778-
dc.description.abstractWe have generated a novel model system for the study of estrogen intervention in normal breast tissue. Nulliparous human breast tissue was implanted into immunocompromised nude mice and treated with high-dose estrogen to simulate the effects of pregnancy. Treatment of mice with human mid-pregnancy levels of 17beta-estradiol for a period of 4 weeks was followed by 4 weeks of withdrawal to mimic involution. Gene expression in the xenograft tissue was then analyzed by real-time reverse transcription-PCR to identify differences between treated and control tissues. Ten genes previously identified as altered by pregnancy in rodent models were found to be differentially expressed in human breast tissue with a > or =1.8-fold up-regulation of CDC42, TGFbeta3, DCN, KRT14, LTF, and AREG and a > or =0.7-fold down-regulation of STAT1, CTGF, IGF1, and VAMP1. Immunohistochemical analysis of archival paraffin-embedded adult premenopausal human breast tissue specimens identified a significantly lower level of expression of STAT1 (P < 0.05, Mann-Whitney U test) in parous compared with age-matched nulliparous tissue (median of 24% compared with 42% epithelial cells positive). We conclude that many of the pregnancy-induced breast cancer-protective changes observed in rodent models also occur in human breast tissue following intervention using human pregnancy levels of estrogen and that STAT1 expression is a potential biomarker of parity-induced breast cancer protection in the human breast.en
dc.language.isoenen
dc.subjectEstrogen Interventionen
dc.subjectBreast Tissueen
dc.subjectMiceen
dc.subjectBreast Canceren
dc.titleNormal breast tissue implanted into athymic nude mice identifies biomarkers of the effects of human pregnancy levels of estrogen.en
dc.typeArticleen
dc.contributor.departmentBreast Biology Group, School of Cancer and Imaging Sciences, Paterson Institute for Cancer Research, University of Manchester, Manchester, United Kingdom.en
dc.identifier.journalCancer Prevention Researchen

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