RGD Reference Report - Endometase/matrilysin-2 in human breast ductal carcinoma in situ and its inhibition by tissue inhibitors of metalloproteinases-2 and -4: a putative role in the initiation of breast cancer invasion. - Rat Genome Database

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Endometase/matrilysin-2 in human breast ductal carcinoma in situ and its inhibition by tissue inhibitors of metalloproteinases-2 and -4: a putative role in the initiation of breast cancer invasion.

Authors: Zhao, YG  Xiao, AZ  Park, HI  Newcomer, RG  Yan, M  Man, YG  Heffelfinger, SC  Sang, QX 
Citation: Zhao YG, etal., Cancer Res. 2004 Jan 15;64(2):590-8.
RGD ID: 2290436
Pubmed: PMID:14744773   (View Abstract at PubMed)

Local disruption of the integrity of both the myoepithelial cell layer and the basement membrane is an indispensable prerequisite for the initiation of invasion and the conversion of human breast ductal carcinoma in situ (DCIS) to infiltrating ductal carcinoma (IDC). We previously reported that human endometase/matrilysin-2/matrix metalloproteinase (MMP) 26-mediated pro-gelatinase B (MMP-9) activation promoted invasion of human prostate carcinoma cells by dissolving basement membrane proteins (Y. G. Zhao et al., J. Biol. Chem., 278: 15056-15064, 2003). Here we report that tissue inhibitor of metalloproteinases (TIMP)-2 and TIMP-4 are potent inhibitors of MMP-26, with apparent K(i) values of 1.6 and 0.62 nM, respectively. TIMP-2 and TIMP-4 also inhibited the activation of pro-MMP-9 by MMP-26 in vitro. The expression levels of MMP-26, MMP-9, TIMP-2, and TIMP-4 proteins in DCIS were significantly higher than those in IDC, atypical intraductal hyperplasia, and normal breast epithelia adjacent to DCIS and IDC by immunohistochemistry and integrated morphometry analysis. Double immunofluorescence labeling and confocal laser scanning microscopy revealed that MMP-26 was colocalized with MMP-9, TIMP-2, and TIMP-4 in DCIS cells. Higher levels of MMP-26 mRNA were also detected in DCIS cells by in situ hybridization.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
ductal carcinoma in situ  IEP 2290436; 2290436; 2290436protein:increased expression:breastRGD 
ductal carcinoma in situ  ISOMMP9 (Homo sapiens)2290436; 2290436protein:increased expression:breastRGD 
ductal carcinoma in situ  ISOTIMP2 (Homo sapiens)2290436; 2290436protein:increased expression:breastRGD 
ductal carcinoma in situ  ISOTIMP4 (Homo sapiens)2290436; 2290436protein:increased expression:breastRGD 

Objects Annotated

Genes (Rattus norvegicus)
Mmp9  (matrix metallopeptidase 9)
Timp2  (TIMP metallopeptidase inhibitor 2)
Timp4  (TIMP metallopeptidase inhibitor 4)

Genes (Mus musculus)
Mmp9  (matrix metallopeptidase 9)
Timp2  (tissue inhibitor of metalloproteinase 2)
Timp4  (tissue inhibitor of metalloproteinase 4)

Genes (Homo sapiens)
MMP9  (matrix metallopeptidase 9)
TIMP2  (TIMP metallopeptidase inhibitor 2)
TIMP4  (TIMP metallopeptidase inhibitor 4)


Additional Information