Matrix metalloproteinase 7 mediates mammary epithelial cell tumorigenesis through the ErbB4 receptor

Conor C. Lynch; Tracy Vargo-Gogola; Michelle D. Martin; Barbara Fingleton; Howard C. Crawford; Lynn M. Matrisian

doi:10.1158/0008-5472.CAN-07-0026

Matrix metalloproteinase 7 mediates mammary epithelial cell tumorigenesis through the ErbB4 receptor

Conor C. Lynch, Tracy Vargo-Gogola, Michelle D. Martin, Barbara Fingleton, Howard C. Crawford, Lynn M. Matrisian

Cancer Biology

Research output: Contribution to journal › Article › peer-review

53 Scopus citations

Abstract

To delineate the role of matrix metalloproteinase 7 (MMP7) in mammary tumorigenesis, MMP7 was expressed in the normal murine mammary gland cell line, c57MG. MMP7 markedly enhanced the growth rate of the c57MG cells in three-dimensional culture and promoted tumor formation in vivo. Subsequent investigation showed that MMP7 (a) up-regulated ErbB4 receptor levels, (b) solubilized the ErbB4 receptor cognate ligand heparin-bound epidermal growth factor, and (c) mediated the proteolytic processing of ErbB4 to yield a soluble intracellular domain (ICD) that localized to the cytoplasm and the nucleus. Furthermore, overexpression of the ErbB4 ICD in the c57MG cell line recapitulated the proliferative effects of MMP7 in vitro and in vivo. These data indicate a novel mechanism for mammary epithelial cell transformation by MMP7.

Original language	English (US)
Pages (from-to)	6760-6767
Number of pages	8
Journal	Cancer research
Volume	67
Issue number	14
DOIs	https://doi.org/10.1158/0008-5472.CAN-07-0026
State	Published - Jul 15 2007

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1158/0008-5472.CAN-07-0026

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title = "Matrix metalloproteinase 7 mediates mammary epithelial cell tumorigenesis through the ErbB4 receptor",

abstract = "To delineate the role of matrix metalloproteinase 7 (MMP7) in mammary tumorigenesis, MMP7 was expressed in the normal murine mammary gland cell line, c57MG. MMP7 markedly enhanced the growth rate of the c57MG cells in three-dimensional culture and promoted tumor formation in vivo. Subsequent investigation showed that MMP7 (a) up-regulated ErbB4 receptor levels, (b) solubilized the ErbB4 receptor cognate ligand heparin-bound epidermal growth factor, and (c) mediated the proteolytic processing of ErbB4 to yield a soluble intracellular domain (ICD) that localized to the cytoplasm and the nucleus. Furthermore, overexpression of the ErbB4 ICD in the c57MG cell line recapitulated the proliferative effects of MMP7 in vitro and in vivo. These data indicate a novel mechanism for mammary epithelial cell transformation by MMP7.",

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AU - Lynch, Conor C.

AU - Vargo-Gogola, Tracy

AU - Martin, Michelle D.

AU - Fingleton, Barbara

AU - Crawford, Howard C.

AU - Matrisian, Lynn M.

PY - 2007/7/15

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AB - To delineate the role of matrix metalloproteinase 7 (MMP7) in mammary tumorigenesis, MMP7 was expressed in the normal murine mammary gland cell line, c57MG. MMP7 markedly enhanced the growth rate of the c57MG cells in three-dimensional culture and promoted tumor formation in vivo. Subsequent investigation showed that MMP7 (a) up-regulated ErbB4 receptor levels, (b) solubilized the ErbB4 receptor cognate ligand heparin-bound epidermal growth factor, and (c) mediated the proteolytic processing of ErbB4 to yield a soluble intracellular domain (ICD) that localized to the cytoplasm and the nucleus. Furthermore, overexpression of the ErbB4 ICD in the c57MG cell line recapitulated the proliferative effects of MMP7 in vitro and in vivo. These data indicate a novel mechanism for mammary epithelial cell transformation by MMP7.

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Matrix metalloproteinase 7 mediates mammary epithelial cell tumorigenesis through the ErbB4 receptor

Abstract

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