The induction of uterine leiomyomas and mammary tumors in transgenic mice expressing polyomavirus (PyV) large T (LT) antigen is associated with the ability of PyV LT antigen to form specific complexes with retinoblastoma and CUTL1 family members

Marc A. Webster, Nathalie Martin-Soudant, Alain Nepveu, Robert Cardiff, William J. Muller

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The inactivation of certain tumor suppressor genes is thought to play an important role in the genesis of a number of tumor types. For example, inactivation of the Retinoblastoma (Rb) tumor suppressor is frequently observed in a proportion of sporadic human breast cancers. While these studies suggest that inactivation of key tumor suppressor genes may play an important role in the induction of mammary cancers, direct evidence supporting this contention is lacking. Because polyomavirus (PyV) Large T (LT) antigen is known to associate with and inactivate certain members of the Rb family (plO5Rb, p107, p130), we have derived transgenic mice which express PyV LT antigen in the mammary epithelium. As expected mammary epithelial-specific expression of PyV LT antigen resulted in the induction of mammary tumors which correlated with their capacity to associate with Rb family members. In addition to mammary carcinomas, female transgenic mice expressing the PyV LT transgene frequently develop uterine leiomyomas. Because loss of heterozygosity involving the human CUTL1 (Cut like 1) gene located at chromosomal position 7q22 has been recently implicated in sporadic human uterine leiomyomas, we tested the hypothesis that PyV LT antigen may also form specific complexes with CUTL1. The results of these analyses revealed that specific complexes of CUTL1 and PYV LT antigen could be detected in both leiomyomas and mammary tumors. Taken together, these observations suggest that PyV LT antigen may be involved in inducing these tumors by sequestering both CUTL1 and Rb growth regulatory proteins.

Original languageEnglish (US)
Pages (from-to)1963-1972
Number of pages10
JournalOncogene
Volume16
Issue number15
DOIs
StatePublished - Apr 16 1998

Fingerprint

Polyomavirus Transforming Antigens
Aptitude
Retinoblastoma
Leiomyoma
Transgenic Mice
Breast Neoplasms
Tumor Suppressor Genes
Breast
Neoplasms
Polyomavirus
Loss of Heterozygosity
Viral Tumor Antigens
Transgenes
Epithelium
Growth
Genes
Proteins

Keywords

  • CUTL1
  • Leiomyomas
  • Mammary tumors
  • Polyomauirus LT
  • Transgenic

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

The induction of uterine leiomyomas and mammary tumors in transgenic mice expressing polyomavirus (PyV) large T (LT) antigen is associated with the ability of PyV LT antigen to form specific complexes with retinoblastoma and CUTL1 family members. / Webster, Marc A.; Martin-Soudant, Nathalie; Nepveu, Alain; Cardiff, Robert; Muller, William J.

In: Oncogene, Vol. 16, No. 15, 16.04.1998, p. 1963-1972.

Research output: Contribution to journalArticle

@article{a3b4ee79b1454031bfe4f143dc3a247a,
title = "The induction of uterine leiomyomas and mammary tumors in transgenic mice expressing polyomavirus (PyV) large T (LT) antigen is associated with the ability of PyV LT antigen to form specific complexes with retinoblastoma and CUTL1 family members",
abstract = "The inactivation of certain tumor suppressor genes is thought to play an important role in the genesis of a number of tumor types. For example, inactivation of the Retinoblastoma (Rb) tumor suppressor is frequently observed in a proportion of sporadic human breast cancers. While these studies suggest that inactivation of key tumor suppressor genes may play an important role in the induction of mammary cancers, direct evidence supporting this contention is lacking. Because polyomavirus (PyV) Large T (LT) antigen is known to associate with and inactivate certain members of the Rb family (plO5Rb, p107, p130), we have derived transgenic mice which express PyV LT antigen in the mammary epithelium. As expected mammary epithelial-specific expression of PyV LT antigen resulted in the induction of mammary tumors which correlated with their capacity to associate with Rb family members. In addition to mammary carcinomas, female transgenic mice expressing the PyV LT transgene frequently develop uterine leiomyomas. Because loss of heterozygosity involving the human CUTL1 (Cut like 1) gene located at chromosomal position 7q22 has been recently implicated in sporadic human uterine leiomyomas, we tested the hypothesis that PyV LT antigen may also form specific complexes with CUTL1. The results of these analyses revealed that specific complexes of CUTL1 and PYV LT antigen could be detected in both leiomyomas and mammary tumors. Taken together, these observations suggest that PyV LT antigen may be involved in inducing these tumors by sequestering both CUTL1 and Rb growth regulatory proteins.",
keywords = "CUTL1, Leiomyomas, Mammary tumors, Polyomauirus LT, Transgenic",
author = "Webster, {Marc A.} and Nathalie Martin-Soudant and Alain Nepveu and Robert Cardiff and Muller, {William J.}",
year = "1998",
month = "4",
day = "16",
doi = "10.1038/sj.onc.1201707",
language = "English (US)",
volume = "16",
pages = "1963--1972",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "15",

}

TY - JOUR

T1 - The induction of uterine leiomyomas and mammary tumors in transgenic mice expressing polyomavirus (PyV) large T (LT) antigen is associated with the ability of PyV LT antigen to form specific complexes with retinoblastoma and CUTL1 family members

AU - Webster, Marc A.

AU - Martin-Soudant, Nathalie

AU - Nepveu, Alain

AU - Cardiff, Robert

AU - Muller, William J.

PY - 1998/4/16

Y1 - 1998/4/16

N2 - The inactivation of certain tumor suppressor genes is thought to play an important role in the genesis of a number of tumor types. For example, inactivation of the Retinoblastoma (Rb) tumor suppressor is frequently observed in a proportion of sporadic human breast cancers. While these studies suggest that inactivation of key tumor suppressor genes may play an important role in the induction of mammary cancers, direct evidence supporting this contention is lacking. Because polyomavirus (PyV) Large T (LT) antigen is known to associate with and inactivate certain members of the Rb family (plO5Rb, p107, p130), we have derived transgenic mice which express PyV LT antigen in the mammary epithelium. As expected mammary epithelial-specific expression of PyV LT antigen resulted in the induction of mammary tumors which correlated with their capacity to associate with Rb family members. In addition to mammary carcinomas, female transgenic mice expressing the PyV LT transgene frequently develop uterine leiomyomas. Because loss of heterozygosity involving the human CUTL1 (Cut like 1) gene located at chromosomal position 7q22 has been recently implicated in sporadic human uterine leiomyomas, we tested the hypothesis that PyV LT antigen may also form specific complexes with CUTL1. The results of these analyses revealed that specific complexes of CUTL1 and PYV LT antigen could be detected in both leiomyomas and mammary tumors. Taken together, these observations suggest that PyV LT antigen may be involved in inducing these tumors by sequestering both CUTL1 and Rb growth regulatory proteins.

AB - The inactivation of certain tumor suppressor genes is thought to play an important role in the genesis of a number of tumor types. For example, inactivation of the Retinoblastoma (Rb) tumor suppressor is frequently observed in a proportion of sporadic human breast cancers. While these studies suggest that inactivation of key tumor suppressor genes may play an important role in the induction of mammary cancers, direct evidence supporting this contention is lacking. Because polyomavirus (PyV) Large T (LT) antigen is known to associate with and inactivate certain members of the Rb family (plO5Rb, p107, p130), we have derived transgenic mice which express PyV LT antigen in the mammary epithelium. As expected mammary epithelial-specific expression of PyV LT antigen resulted in the induction of mammary tumors which correlated with their capacity to associate with Rb family members. In addition to mammary carcinomas, female transgenic mice expressing the PyV LT transgene frequently develop uterine leiomyomas. Because loss of heterozygosity involving the human CUTL1 (Cut like 1) gene located at chromosomal position 7q22 has been recently implicated in sporadic human uterine leiomyomas, we tested the hypothesis that PyV LT antigen may also form specific complexes with CUTL1. The results of these analyses revealed that specific complexes of CUTL1 and PYV LT antigen could be detected in both leiomyomas and mammary tumors. Taken together, these observations suggest that PyV LT antigen may be involved in inducing these tumors by sequestering both CUTL1 and Rb growth regulatory proteins.

KW - CUTL1

KW - Leiomyomas

KW - Mammary tumors

KW - Polyomauirus LT

KW - Transgenic

UR - http://www.scopus.com/inward/record.url?scp=0032537012&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032537012&partnerID=8YFLogxK

U2 - 10.1038/sj.onc.1201707

DO - 10.1038/sj.onc.1201707

M3 - Article

C2 - 9591780

AN - SCOPUS:0032537012

VL - 16

SP - 1963

EP - 1972

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 15

ER -