MUC1 overexpression results in mammary gland tumorigenesis and prolonged alveolar differentiation

Joyce Schroeder, Azzah Al Masri, Melissa C. Adriance, Jennifer C. Tessier, Kari L. Kotlarczyk, Melissa C. Thompson, Sandra J. Gendler

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

MUC1 is a transmembrane mucin that was initially cloned from malignant mammary epithelial cells as a tumor antigen. More than 90% of human breast carcinomas overexpress MUC1. Numerous studies have demonstrated an interaction between MUC1 and other oncogenic proteins such as β-catenin, erbB receptors and c-Src, but a functional role for MUC1 in transformation has not been identified. We previously reported the development of transgenic mice that overexpress human MUC1 in the mouse mammary gland (MMTV-MUC1). Analysis of these transgenic mice at an early age demonstrated the ability of MUC1 to potentiate EGF-dependent activation of MAP kinase signaling pathways in the lactating mammary gland. We now report that multiparous MMTV-MUC1 transgenic mice stochastically develop unifocal mammary gland carcinomas late in life. Molecular analysis of these tumors shows a tumor-specific coimmunoprecipitation between MUC1 and β-catenin. Examination of the contralateral glands in MMTV-MUC1 transgenics demonstrates that the development of frank carcinomas is accompanied by a failure of multiparous glands to undergo postlactational involution. Furthermore, uniparous MMTV-MUC1 transgenic mice display decreased postlactational apoptosis, elevated whey acidic protein expression and aberrant pErk2 activation. These findings are the first to determine that MUC1 overexpression promotes in vivo transformation of the mammary gland.

Original languageEnglish (US)
Pages (from-to)5739-5747
Number of pages9
JournalOncogene
Volume23
Issue number34
DOIs
StatePublished - Jul 29 2004

Fingerprint

Human Mammary Glands
Transgenic Mice
Carcinogenesis
Catenins
Breast Neoplasms
MAP Kinase Signaling System
Neoplasm Antigens
Mucins
Epidermal Growth Factor
Neoplasms
Breast
Epithelial Cells
Apoptosis
Carcinoma
Proteins

Keywords

  • Apoptosis
  • Breast cancer
  • Involution
  • Mammary gland
  • Mucin

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Schroeder, J., Al Masri, A., Adriance, M. C., Tessier, J. C., Kotlarczyk, K. L., Thompson, M. C., & Gendler, S. J. (2004). MUC1 overexpression results in mammary gland tumorigenesis and prolonged alveolar differentiation. Oncogene, 23(34), 5739-5747. https://doi.org/10.1038/sj.onc.1207713

MUC1 overexpression results in mammary gland tumorigenesis and prolonged alveolar differentiation. / Schroeder, Joyce; Al Masri, Azzah; Adriance, Melissa C.; Tessier, Jennifer C.; Kotlarczyk, Kari L.; Thompson, Melissa C.; Gendler, Sandra J.

In: Oncogene, Vol. 23, No. 34, 29.07.2004, p. 5739-5747.

Research output: Contribution to journalArticle

Schroeder, J, Al Masri, A, Adriance, MC, Tessier, JC, Kotlarczyk, KL, Thompson, MC & Gendler, SJ 2004, 'MUC1 overexpression results in mammary gland tumorigenesis and prolonged alveolar differentiation', Oncogene, vol. 23, no. 34, pp. 5739-5747. https://doi.org/10.1038/sj.onc.1207713
Schroeder J, Al Masri A, Adriance MC, Tessier JC, Kotlarczyk KL, Thompson MC et al. MUC1 overexpression results in mammary gland tumorigenesis and prolonged alveolar differentiation. Oncogene. 2004 Jul 29;23(34):5739-5747. https://doi.org/10.1038/sj.onc.1207713
Schroeder, Joyce ; Al Masri, Azzah ; Adriance, Melissa C. ; Tessier, Jennifer C. ; Kotlarczyk, Kari L. ; Thompson, Melissa C. ; Gendler, Sandra J. / MUC1 overexpression results in mammary gland tumorigenesis and prolonged alveolar differentiation. In: Oncogene. 2004 ; Vol. 23, No. 34. pp. 5739-5747.
@article{522b010dd14d4626920b368adc63b646,
title = "MUC1 overexpression results in mammary gland tumorigenesis and prolonged alveolar differentiation",
abstract = "MUC1 is a transmembrane mucin that was initially cloned from malignant mammary epithelial cells as a tumor antigen. More than 90{\%} of human breast carcinomas overexpress MUC1. Numerous studies have demonstrated an interaction between MUC1 and other oncogenic proteins such as β-catenin, erbB receptors and c-Src, but a functional role for MUC1 in transformation has not been identified. We previously reported the development of transgenic mice that overexpress human MUC1 in the mouse mammary gland (MMTV-MUC1). Analysis of these transgenic mice at an early age demonstrated the ability of MUC1 to potentiate EGF-dependent activation of MAP kinase signaling pathways in the lactating mammary gland. We now report that multiparous MMTV-MUC1 transgenic mice stochastically develop unifocal mammary gland carcinomas late in life. Molecular analysis of these tumors shows a tumor-specific coimmunoprecipitation between MUC1 and β-catenin. Examination of the contralateral glands in MMTV-MUC1 transgenics demonstrates that the development of frank carcinomas is accompanied by a failure of multiparous glands to undergo postlactational involution. Furthermore, uniparous MMTV-MUC1 transgenic mice display decreased postlactational apoptosis, elevated whey acidic protein expression and aberrant pErk2 activation. These findings are the first to determine that MUC1 overexpression promotes in vivo transformation of the mammary gland.",
keywords = "Apoptosis, Breast cancer, Involution, Mammary gland, Mucin",
author = "Joyce Schroeder and {Al Masri}, Azzah and Adriance, {Melissa C.} and Tessier, {Jennifer C.} and Kotlarczyk, {Kari L.} and Thompson, {Melissa C.} and Gendler, {Sandra J.}",
year = "2004",
month = "7",
day = "29",
doi = "10.1038/sj.onc.1207713",
language = "English (US)",
volume = "23",
pages = "5739--5747",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "34",

}

TY - JOUR

T1 - MUC1 overexpression results in mammary gland tumorigenesis and prolonged alveolar differentiation

AU - Schroeder, Joyce

AU - Al Masri, Azzah

AU - Adriance, Melissa C.

AU - Tessier, Jennifer C.

AU - Kotlarczyk, Kari L.

AU - Thompson, Melissa C.

AU - Gendler, Sandra J.

PY - 2004/7/29

Y1 - 2004/7/29

N2 - MUC1 is a transmembrane mucin that was initially cloned from malignant mammary epithelial cells as a tumor antigen. More than 90% of human breast carcinomas overexpress MUC1. Numerous studies have demonstrated an interaction between MUC1 and other oncogenic proteins such as β-catenin, erbB receptors and c-Src, but a functional role for MUC1 in transformation has not been identified. We previously reported the development of transgenic mice that overexpress human MUC1 in the mouse mammary gland (MMTV-MUC1). Analysis of these transgenic mice at an early age demonstrated the ability of MUC1 to potentiate EGF-dependent activation of MAP kinase signaling pathways in the lactating mammary gland. We now report that multiparous MMTV-MUC1 transgenic mice stochastically develop unifocal mammary gland carcinomas late in life. Molecular analysis of these tumors shows a tumor-specific coimmunoprecipitation between MUC1 and β-catenin. Examination of the contralateral glands in MMTV-MUC1 transgenics demonstrates that the development of frank carcinomas is accompanied by a failure of multiparous glands to undergo postlactational involution. Furthermore, uniparous MMTV-MUC1 transgenic mice display decreased postlactational apoptosis, elevated whey acidic protein expression and aberrant pErk2 activation. These findings are the first to determine that MUC1 overexpression promotes in vivo transformation of the mammary gland.

AB - MUC1 is a transmembrane mucin that was initially cloned from malignant mammary epithelial cells as a tumor antigen. More than 90% of human breast carcinomas overexpress MUC1. Numerous studies have demonstrated an interaction between MUC1 and other oncogenic proteins such as β-catenin, erbB receptors and c-Src, but a functional role for MUC1 in transformation has not been identified. We previously reported the development of transgenic mice that overexpress human MUC1 in the mouse mammary gland (MMTV-MUC1). Analysis of these transgenic mice at an early age demonstrated the ability of MUC1 to potentiate EGF-dependent activation of MAP kinase signaling pathways in the lactating mammary gland. We now report that multiparous MMTV-MUC1 transgenic mice stochastically develop unifocal mammary gland carcinomas late in life. Molecular analysis of these tumors shows a tumor-specific coimmunoprecipitation between MUC1 and β-catenin. Examination of the contralateral glands in MMTV-MUC1 transgenics demonstrates that the development of frank carcinomas is accompanied by a failure of multiparous glands to undergo postlactational involution. Furthermore, uniparous MMTV-MUC1 transgenic mice display decreased postlactational apoptosis, elevated whey acidic protein expression and aberrant pErk2 activation. These findings are the first to determine that MUC1 overexpression promotes in vivo transformation of the mammary gland.

KW - Apoptosis

KW - Breast cancer

KW - Involution

KW - Mammary gland

KW - Mucin

UR - http://www.scopus.com/inward/record.url?scp=4143099166&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4143099166&partnerID=8YFLogxK

U2 - 10.1038/sj.onc.1207713

DO - 10.1038/sj.onc.1207713

M3 - Article

C2 - 15221004

AN - SCOPUS:4143099166

VL - 23

SP - 5739

EP - 5747

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 34

ER -