The dual function steroid receptor coactivator/ubiquitin protein-ligase integrator E6-AP is overexpressed in mouse mammary tumorigenesis

L. Sivaraman, Zafar Nawaz, D. Medina, O. M. Conneely, B. W. O'Malley

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Steroid receptor coactivator and corepressor proteins are important mediators of steroid receptor function. Changes in the expression or activity of these limiting cofactors can contribute to the etiology of steroidal cancers. Using a mouse mammary model of multistage tumorigenesis we have examined whether the expression of select steroid receptor coactivators is altered. The 10 kb transcript of the novel dual function steroid receptor coactivator/ubiquitin protein-ligase integrator E6-AP is overexpressed 2.5-4.5 fold in the mammary tumors but not in the precursor steps of tumorigenesis; that is, immortal ductal and alveolar hyperplastic outgrowths. The over expression is striking because the 10 kb transcript is expressed to variable levels in other wild type tissues like the uterus, ovary, testis, kidney and brain but is undetectable in normal virgin mammary gland and the prostate gland. The E6-AP overexpression in the mammary tumors in substantiated by western blot analysis and immunohistochemical analysis. Absence of ER and PR in these tumors in the presence of high levels of E6-AP could contribute to steroid receptor-independent function and tumorigenesis. There is no obvious correlation between p53 (a well-characterized substrate of E6-AP) status (wt vs. mutant) and levels of E6-AP in the mouse mammary tumors.

Original languageEnglish
Pages (from-to)185-195
Number of pages11
JournalBreast Cancer Research and Treatment
Volume62
Issue number3
DOIs
StatePublished - Nov 11 2000
Externally publishedYes

Fingerprint

Ubiquitin-Protein Ligases
Steroid Receptors
Carcinogenesis
Breast
Breast Neoplasms
Co-Repressor Proteins
Human Mammary Glands
Uterus
Testis
Prostate
Ovary
Neoplasms
Western Blotting
Kidney
Brain

Keywords

  • E6-AP
  • Mammary gland
  • Mammary tumorigenesis
  • Steroid receptor coactivators

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

The dual function steroid receptor coactivator/ubiquitin protein-ligase integrator E6-AP is overexpressed in mouse mammary tumorigenesis. / Sivaraman, L.; Nawaz, Zafar; Medina, D.; Conneely, O. M.; O'Malley, B. W.

In: Breast Cancer Research and Treatment, Vol. 62, No. 3, 11.11.2000, p. 185-195.

Research output: Contribution to journalArticle

@article{6fad04f7c65f446e990b1a64e7b4c89e,
title = "The dual function steroid receptor coactivator/ubiquitin protein-ligase integrator E6-AP is overexpressed in mouse mammary tumorigenesis",
abstract = "Steroid receptor coactivator and corepressor proteins are important mediators of steroid receptor function. Changes in the expression or activity of these limiting cofactors can contribute to the etiology of steroidal cancers. Using a mouse mammary model of multistage tumorigenesis we have examined whether the expression of select steroid receptor coactivators is altered. The 10 kb transcript of the novel dual function steroid receptor coactivator/ubiquitin protein-ligase integrator E6-AP is overexpressed 2.5-4.5 fold in the mammary tumors but not in the precursor steps of tumorigenesis; that is, immortal ductal and alveolar hyperplastic outgrowths. The over expression is striking because the 10 kb transcript is expressed to variable levels in other wild type tissues like the uterus, ovary, testis, kidney and brain but is undetectable in normal virgin mammary gland and the prostate gland. The E6-AP overexpression in the mammary tumors in substantiated by western blot analysis and immunohistochemical analysis. Absence of ER and PR in these tumors in the presence of high levels of E6-AP could contribute to steroid receptor-independent function and tumorigenesis. There is no obvious correlation between p53 (a well-characterized substrate of E6-AP) status (wt vs. mutant) and levels of E6-AP in the mouse mammary tumors.",
keywords = "E6-AP, Mammary gland, Mammary tumorigenesis, Steroid receptor coactivators",
author = "L. Sivaraman and Zafar Nawaz and D. Medina and Conneely, {O. M.} and O'Malley, {B. W.}",
year = "2000",
month = "11",
day = "11",
doi = "10.1023/A:1006410111706",
language = "English",
volume = "62",
pages = "185--195",
journal = "Breast Cancer Research and Treatment",
issn = "0167-6806",
publisher = "Springer New York",
number = "3",

}

TY - JOUR

T1 - The dual function steroid receptor coactivator/ubiquitin protein-ligase integrator E6-AP is overexpressed in mouse mammary tumorigenesis

AU - Sivaraman, L.

AU - Nawaz, Zafar

AU - Medina, D.

AU - Conneely, O. M.

AU - O'Malley, B. W.

PY - 2000/11/11

Y1 - 2000/11/11

N2 - Steroid receptor coactivator and corepressor proteins are important mediators of steroid receptor function. Changes in the expression or activity of these limiting cofactors can contribute to the etiology of steroidal cancers. Using a mouse mammary model of multistage tumorigenesis we have examined whether the expression of select steroid receptor coactivators is altered. The 10 kb transcript of the novel dual function steroid receptor coactivator/ubiquitin protein-ligase integrator E6-AP is overexpressed 2.5-4.5 fold in the mammary tumors but not in the precursor steps of tumorigenesis; that is, immortal ductal and alveolar hyperplastic outgrowths. The over expression is striking because the 10 kb transcript is expressed to variable levels in other wild type tissues like the uterus, ovary, testis, kidney and brain but is undetectable in normal virgin mammary gland and the prostate gland. The E6-AP overexpression in the mammary tumors in substantiated by western blot analysis and immunohistochemical analysis. Absence of ER and PR in these tumors in the presence of high levels of E6-AP could contribute to steroid receptor-independent function and tumorigenesis. There is no obvious correlation between p53 (a well-characterized substrate of E6-AP) status (wt vs. mutant) and levels of E6-AP in the mouse mammary tumors.

AB - Steroid receptor coactivator and corepressor proteins are important mediators of steroid receptor function. Changes in the expression or activity of these limiting cofactors can contribute to the etiology of steroidal cancers. Using a mouse mammary model of multistage tumorigenesis we have examined whether the expression of select steroid receptor coactivators is altered. The 10 kb transcript of the novel dual function steroid receptor coactivator/ubiquitin protein-ligase integrator E6-AP is overexpressed 2.5-4.5 fold in the mammary tumors but not in the precursor steps of tumorigenesis; that is, immortal ductal and alveolar hyperplastic outgrowths. The over expression is striking because the 10 kb transcript is expressed to variable levels in other wild type tissues like the uterus, ovary, testis, kidney and brain but is undetectable in normal virgin mammary gland and the prostate gland. The E6-AP overexpression in the mammary tumors in substantiated by western blot analysis and immunohistochemical analysis. Absence of ER and PR in these tumors in the presence of high levels of E6-AP could contribute to steroid receptor-independent function and tumorigenesis. There is no obvious correlation between p53 (a well-characterized substrate of E6-AP) status (wt vs. mutant) and levels of E6-AP in the mouse mammary tumors.

KW - E6-AP

KW - Mammary gland

KW - Mammary tumorigenesis

KW - Steroid receptor coactivators

UR - http://www.scopus.com/inward/record.url?scp=0033765996&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033765996&partnerID=8YFLogxK

U2 - 10.1023/A:1006410111706

DO - 10.1023/A:1006410111706

M3 - Article

VL - 62

SP - 185

EP - 195

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

SN - 0167-6806

IS - 3

ER -