Polyomavirus middle T-induced mammary intraepithelial neoplasia outgrowths

Single origin, divergent evolution, and multiple outcomes

Jeannie E. Maglione, Erik T. McGoldrick, Lawrence J T Young, Ruria Namba, Jeffrey Gregg, Lin Liu, Drew Moghanaki, Lesley G. Ellis, Alexander D Borowsky, Robert Cardiff, Carol L. MacLeod

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

The development of models to investigate the pathobiology of premalignant breast lesions is a critical prerequisite for development of breast cancer prevention and early intervention strategies. Using tissue transplantation techniques, we modified the widely used polyomavirus middle T (PyV-mT) transgenic mouse model of breast cancer to study the premalignant stages of tumorigenesis. Premalignant atypical lesions were isolated from PyV-mT transgenic mice and used to generate two sets of three mammary intraepithelial neoplasia (MIN) outgrowth lines. Investigation of these six unique lines, each of which fulfills the criteria for MIN, has provided new information regarding the biology of PyV-mT-induced neoplasia. Although expression of the PyV-mT transgene was the primary initiating event for all lines, they exhibited different tumor latencies, metastatic potentials, and morphologies. Six distinguishable morphologic patterns of differentiation were identified within the premalignant outgrowths that are likely to represent several tumorigenic pathways. Further, several tumor phenotypes developed from each line and the tumors developing from the six lines had different metastatic potentials. These observations are consistent with the hypothesis that distinct pathways of PyV-mT-initiated neoplastic progression lead to different outcomes with respect to latency and metastasis. The MIN outgrowth lines share several characteristics with precursors of human breast cancer including the observation that gene expression profiles of tumors are more similar to those of the MIN outgrowth line outgrowth from which they developed than to other tumors. These lines provide an opportunity to study the full range of events occurring secondary to PyV-mT expression in the mammary gland.

Original languageEnglish (US)
Pages (from-to)941-953
Number of pages13
JournalMolecular Cancer Therapeutics
Volume3
Issue number8
StatePublished - Aug 2004

Fingerprint

Polyomavirus
Breast
Neoplasms
Breast Neoplasms
Transgenic Mice
Tissue Transplantation
Human Mammary Glands
Transgenes
Transcriptome
Carcinogenesis
Neoplasm Metastasis
Phenotype

ASJC Scopus subject areas

  • Oncology
  • Drug Discovery
  • Pharmacology

Cite this

Maglione, J. E., McGoldrick, E. T., Young, L. J. T., Namba, R., Gregg, J., Liu, L., ... MacLeod, C. L. (2004). Polyomavirus middle T-induced mammary intraepithelial neoplasia outgrowths: Single origin, divergent evolution, and multiple outcomes. Molecular Cancer Therapeutics, 3(8), 941-953.

Polyomavirus middle T-induced mammary intraepithelial neoplasia outgrowths : Single origin, divergent evolution, and multiple outcomes. / Maglione, Jeannie E.; McGoldrick, Erik T.; Young, Lawrence J T; Namba, Ruria; Gregg, Jeffrey; Liu, Lin; Moghanaki, Drew; Ellis, Lesley G.; Borowsky, Alexander D; Cardiff, Robert; MacLeod, Carol L.

In: Molecular Cancer Therapeutics, Vol. 3, No. 8, 08.2004, p. 941-953.

Research output: Contribution to journalArticle

Maglione, JE, McGoldrick, ET, Young, LJT, Namba, R, Gregg, J, Liu, L, Moghanaki, D, Ellis, LG, Borowsky, AD, Cardiff, R & MacLeod, CL 2004, 'Polyomavirus middle T-induced mammary intraepithelial neoplasia outgrowths: Single origin, divergent evolution, and multiple outcomes', Molecular Cancer Therapeutics, vol. 3, no. 8, pp. 941-953.
Maglione, Jeannie E. ; McGoldrick, Erik T. ; Young, Lawrence J T ; Namba, Ruria ; Gregg, Jeffrey ; Liu, Lin ; Moghanaki, Drew ; Ellis, Lesley G. ; Borowsky, Alexander D ; Cardiff, Robert ; MacLeod, Carol L. / Polyomavirus middle T-induced mammary intraepithelial neoplasia outgrowths : Single origin, divergent evolution, and multiple outcomes. In: Molecular Cancer Therapeutics. 2004 ; Vol. 3, No. 8. pp. 941-953.
@article{31258bacb4c14e48ad98dba25fbfe4d1,
title = "Polyomavirus middle T-induced mammary intraepithelial neoplasia outgrowths: Single origin, divergent evolution, and multiple outcomes",
abstract = "The development of models to investigate the pathobiology of premalignant breast lesions is a critical prerequisite for development of breast cancer prevention and early intervention strategies. Using tissue transplantation techniques, we modified the widely used polyomavirus middle T (PyV-mT) transgenic mouse model of breast cancer to study the premalignant stages of tumorigenesis. Premalignant atypical lesions were isolated from PyV-mT transgenic mice and used to generate two sets of three mammary intraepithelial neoplasia (MIN) outgrowth lines. Investigation of these six unique lines, each of which fulfills the criteria for MIN, has provided new information regarding the biology of PyV-mT-induced neoplasia. Although expression of the PyV-mT transgene was the primary initiating event for all lines, they exhibited different tumor latencies, metastatic potentials, and morphologies. Six distinguishable morphologic patterns of differentiation were identified within the premalignant outgrowths that are likely to represent several tumorigenic pathways. Further, several tumor phenotypes developed from each line and the tumors developing from the six lines had different metastatic potentials. These observations are consistent with the hypothesis that distinct pathways of PyV-mT-initiated neoplastic progression lead to different outcomes with respect to latency and metastasis. The MIN outgrowth lines share several characteristics with precursors of human breast cancer including the observation that gene expression profiles of tumors are more similar to those of the MIN outgrowth line outgrowth from which they developed than to other tumors. These lines provide an opportunity to study the full range of events occurring secondary to PyV-mT expression in the mammary gland.",
author = "Maglione, {Jeannie E.} and McGoldrick, {Erik T.} and Young, {Lawrence J T} and Ruria Namba and Jeffrey Gregg and Lin Liu and Drew Moghanaki and Ellis, {Lesley G.} and Borowsky, {Alexander D} and Robert Cardiff and MacLeod, {Carol L.}",
year = "2004",
month = "8",
language = "English (US)",
volume = "3",
pages = "941--953",
journal = "Molecular Cancer Therapeutics",
issn = "1535-7163",
publisher = "American Association for Cancer Research Inc.",
number = "8",

}

TY - JOUR

T1 - Polyomavirus middle T-induced mammary intraepithelial neoplasia outgrowths

T2 - Single origin, divergent evolution, and multiple outcomes

AU - Maglione, Jeannie E.

AU - McGoldrick, Erik T.

AU - Young, Lawrence J T

AU - Namba, Ruria

AU - Gregg, Jeffrey

AU - Liu, Lin

AU - Moghanaki, Drew

AU - Ellis, Lesley G.

AU - Borowsky, Alexander D

AU - Cardiff, Robert

AU - MacLeod, Carol L.

PY - 2004/8

Y1 - 2004/8

N2 - The development of models to investigate the pathobiology of premalignant breast lesions is a critical prerequisite for development of breast cancer prevention and early intervention strategies. Using tissue transplantation techniques, we modified the widely used polyomavirus middle T (PyV-mT) transgenic mouse model of breast cancer to study the premalignant stages of tumorigenesis. Premalignant atypical lesions were isolated from PyV-mT transgenic mice and used to generate two sets of three mammary intraepithelial neoplasia (MIN) outgrowth lines. Investigation of these six unique lines, each of which fulfills the criteria for MIN, has provided new information regarding the biology of PyV-mT-induced neoplasia. Although expression of the PyV-mT transgene was the primary initiating event for all lines, they exhibited different tumor latencies, metastatic potentials, and morphologies. Six distinguishable morphologic patterns of differentiation were identified within the premalignant outgrowths that are likely to represent several tumorigenic pathways. Further, several tumor phenotypes developed from each line and the tumors developing from the six lines had different metastatic potentials. These observations are consistent with the hypothesis that distinct pathways of PyV-mT-initiated neoplastic progression lead to different outcomes with respect to latency and metastasis. The MIN outgrowth lines share several characteristics with precursors of human breast cancer including the observation that gene expression profiles of tumors are more similar to those of the MIN outgrowth line outgrowth from which they developed than to other tumors. These lines provide an opportunity to study the full range of events occurring secondary to PyV-mT expression in the mammary gland.

AB - The development of models to investigate the pathobiology of premalignant breast lesions is a critical prerequisite for development of breast cancer prevention and early intervention strategies. Using tissue transplantation techniques, we modified the widely used polyomavirus middle T (PyV-mT) transgenic mouse model of breast cancer to study the premalignant stages of tumorigenesis. Premalignant atypical lesions were isolated from PyV-mT transgenic mice and used to generate two sets of three mammary intraepithelial neoplasia (MIN) outgrowth lines. Investigation of these six unique lines, each of which fulfills the criteria for MIN, has provided new information regarding the biology of PyV-mT-induced neoplasia. Although expression of the PyV-mT transgene was the primary initiating event for all lines, they exhibited different tumor latencies, metastatic potentials, and morphologies. Six distinguishable morphologic patterns of differentiation were identified within the premalignant outgrowths that are likely to represent several tumorigenic pathways. Further, several tumor phenotypes developed from each line and the tumors developing from the six lines had different metastatic potentials. These observations are consistent with the hypothesis that distinct pathways of PyV-mT-initiated neoplastic progression lead to different outcomes with respect to latency and metastasis. The MIN outgrowth lines share several characteristics with precursors of human breast cancer including the observation that gene expression profiles of tumors are more similar to those of the MIN outgrowth line outgrowth from which they developed than to other tumors. These lines provide an opportunity to study the full range of events occurring secondary to PyV-mT expression in the mammary gland.

UR - http://www.scopus.com/inward/record.url?scp=4444238684&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4444238684&partnerID=8YFLogxK

M3 - Article

VL - 3

SP - 941

EP - 953

JO - Molecular Cancer Therapeutics

JF - Molecular Cancer Therapeutics

SN - 1535-7163

IS - 8

ER -