HER-2/neu x aromatase double transgenic mice model: the effects of aromatase overexpression on mammary tumorigenesis.

HER-2/neu x aromatase double transgenic mice model: the effects of aromatase overexpression on mammary tumorigenesis. Research Abstract Details 

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HER-2/neu x aromatase double transgenic mice model: the effects of aromatase overexpression on mammary tumorigenesis. Abstract Text:

Rajeshwar Rao Tekmal,Hareesh B Nair,Rao P Perla,Nameer Kirma,

A majority of breast cancers are hormone-responsive, and require estrogen for growth, and respond to hormonal therapy that blocks estrogen receptor action. Breast tumors with low levels of or completely lacking estrogen receptor fail to respond to antiestrogen therapy yet require estrogen for tumor initiation. To address the importance of local estrogen in oncogene-mediated breast tumorigenesis, we have crossed MMTV-aromatase with MMTV-HER2/neu and examined the incidence of breast cancer in double transgenic mice in comparison with parental strains. Double transgenic mice show normal mammary development and express both transgenes at similar levels to that of parental strains. Tumor incidence in double transgenic mice (<5%) decreased compared to HER2/neu mice (>65%). In addition to a significant decrease in tumorigenesis, these mice expressed ERalpha as well as high levels of ERbeta along with decreased levels of cyclin D1 and phosphorylated pRb among other changes. Furthermore, experiments using THC (ERalpha-agonist and ERbeta-antagonist) clearly demonstrate the critical role of ERbeta in HER2/neu-mediated tumorigenesis. These studies provide the first genetic evidence that estrogen receptor, mainly ERbeta than ERalpha and its dependent changes play an important role in regulating mammary tumorigenesis. These findings provide further evidence for development and testing of novel therapeutic approaches based on selective regulation of estrogen receptors (ERalpha and beta)-dependent actions for the treatment and prevention of breast cancers.

HER-2/neu x aromatase double transgenic mice model: the effects of aromatase overexpression on mammary tumorigenesis. Publishing Authors By Initials

RR Tekmal,HB Nair,RP Perla,N Kirma,

For similar proteins: dna-binding proteins: retinoblastoma protein research abstracts see: proteins: dna-binding proteins: retinoblastoma protein research

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HER-2/neu x aromatase double transgenic mice model: the effects of aromatase overexpression on mammary tumorigenesis. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The Journal of steroid biochemistry and molecular

VOLUME: 106

Page Numbers: 111-8

Journal Abbreviation: J. Steroid Biochem. Mol. Biol.

ISSN: 0960-0760

DAY: 24

MONTH: 05

YEAR: 2007

HER-2/neu x aromatase double transgenic mice model: the effects of aromatase overexpression on mammary tumorigenesis. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9015483

HER-2/neu x aromatase double transgenic mice model: the effects of aromatase overexpression on mammary tumorigenesis. Keywords Mesh Terms:

KEYWORDS: Retinoblastoma Protein

MESH TERMS: metabolism

Chemical & Substance for Abstract: HER-2/neu x aromatase double transgenic mice model: the effects of aromatase overexpression on mammary tumorigenesis. Information

Substance Name: Receptor, erbB-2

Registry Number: EC 2.7.1.112

Grant and Affiliation Information for HER-2/neu x aromatase double transgenic mice model: the effects of aromatase overexpression on mammary tumorigenesis.

AFFILIATION: Department of Obstetrics and Gynecology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. tekmal@uthscsa.edu

Country: England

AGENCY: United States NCI

GRANT: P30CA54174

ACRONYM: CA

MEDLINETA: J Steroid Biochem Mol Biol

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