Reference SummaryRudolph-Owen LA, Cancer Res 1998 Dec 1;58(23):5500-6

Title

The matrix metalloproteinase matrilysin influences early-stage mammary tumorigenesis.

Authors

Rudolph-Owen LA; Chan R; Muller WJ; Matrisian LM

Journal

Cancer Res

Volume

58

Issue

23

Year

1998

Pages

5500-6

Abstract

Overexpression of the epithelial specific matrix metalloproteinase matrilysin (MAT) has been correlated with enhanced tumorigenicity and tumor cell invasion using in vitro model systems. We have determined the effects of MAT expression on the development of mammary tumorigenesis using transgenic mice that express human MAT under the control of the mouse mammary tumor virus (MMTV)-long terminal repeat promoter/enhancer. Examination of mammary glands from multiparous MMTV-MAT animals revealed the development of premalignant hyperplastic alveolar nodules in 50% of aged females. MMTV-MAT mice were mated with MMTV-neu transgenic mice to determine the effect of MAT on neu-induced mammary tumorigenesis. Bigenic MMTV-MAT/neu female offspring developed primary mammary tumors approximately 13 weeks earlier than did MMTV-neu controls. The mechanism of enhanced neu-induced tumorigenesis was explored. No discernible difference in Neu receptor dimerization or activation was detected in MMTV-MAT/neu tumors or mammary glands compared to MMTV-neu controls. A similar percentage of MMTV-MAT/neu and MMTV-neu tumors acquired deletions in the neu transgene, which have previously been shown to result in constitutive receptor activation. The presence of premalignant nodules and the accelerated development of oncogene-induced mammary tumors suggest that expression of MAT in the mammary epithelium contributes to early-stage mammary tumorigenesis.

Links

J:51367 – MGI References
9850086 – National Library of Medicine/PubMed

Strain Notes

Strain Note
FVB/N-Tg(MMTV-MAT)3Lmm Beta-casein protein was observed in the mammary glands of virgin mice.
Human MAT was expressed in the epithelium of developing and adult mammary glands.

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
FVB/N-Tg(MMTVneu)202Mul Mammary gland adenocarcinoma Mammary gland

50 - 79

FVB/N-Tg(MMTV-MAT)3Lmm Tg(MMTVneu)202Mul Mammary gland adenocarcinoma Mammary gland

50 - 100

FVB/N-Tg(MMTV-MAT)3Lmm Mammary gland hyperplasia Mammary gland

50

FVB/N Mammary gland hyperplasia Mammary gland

0

FVB/N-Tg(MMTV-MAT)3Lmm Mammary gland tumor Mammary gland

0