D 2012

Regulation of cathepsin D and MMP1/9 by c-Myb is a novel mechanism of the matrix-specific breast cancer cell invasion

KNOPFOVÁ, Lucia, Petr BENEŠ, Lucie PEKARČÍKOVÁ, Markéta HERMANOVÁ, Michal MASAŘÍK et. al.

Basic information

Original name

Regulation of cathepsin D and MMP1/9 by c-Myb is a novel mechanism of the matrix-specific breast cancer cell invasion

Name in Czech

c-Myb reguluje MMP1/9 a cathepsin D - nový mechanismus matrix-dependentní invaze prsních nádorů

Authors

Edition

Cavtat, Dubrovnik, Cellular Signaling and Molecular Medicine, p. 131-131, 2012

Publisher

EMBO

Other information

Language

English

Type of outcome

Stať ve sborníku

Field of Study

Genetics and molecular biology

Confidentiality degree

není předmětem státního či obchodního tajemství

Organization unit

Faculty of Science

Keywords in English

myb breast carcinoma metastasis organotropism

Tags

Tags

International impact
Změněno: 14/8/2012 14:42, prof. RNDr. Jan Šmarda, CSc.

Abstract

V originále

There are conflicting results concerning the c-Myb function in breast cancer. Both oncogenic and tumor-suppressing effects of c-Myb in breast cancer have been recently described. The aim of this study is to elucidate a specific role of c-Myb in control of breast cancer cell invasion. We report that ectopically expressed c-Myb enhances migration of human MDA-MB-231 and mouse 4T1 mammary cancer cells and their ability to invade Matrigel but not the collagen I matrix in vitro. Invasive behavior of breast cancer cells in vivo was determined in a syngeneic mouse mammary tumor model using 4T1 cells. c-myb overexpression in 4T1 cells injected into the mammary fat pads delayed the growth of mammary tumors in BALB/c mice and affected the metastatic potential of breast cancer cells in an organ-specific manner. c-Myb strongly increased the expression/activity of cathepsin D and matrix metalloproteinase (MMP) 9 (92-kDa gelatinase) and significantly downregulated MMP1 (interstitial collagenase). Differential expression of these specific proteases induced by c-Myb was suggested as a mechanism of matrix-specific cell invasion. This study identified c-Myb as a matrix-dependent modifier of invasive breast tumor cell functions. These findings provide new clues for understanding of the oncogenic/tumor-suppressing functions of c-Myb.

Links

GA301/09/1115, research and development project
Name: Úloha proteinů c-Myb a Cox-2 při tvorbě střevních nádorů
Investor: Czech Science Foundation, The role of c-Myb and Cox-2 proteins in colon carcinogenesis
GD204/08/H054, research and development project
Name: Molekulární mechanismy proliferace a diferenciace buněk
Investor: Czech Science Foundation, Molecular mechanisms of the cell proliferation and differentiation
MSM0021622415, plan (intention)
Name: Molekulární podstata buněčných a tkáňových regulací
Investor: Ministry of Education, Youth and Sports of the CR, Molecular basis of cell and tissue regulations
MUNI/C/0968/2010, interní kód MU
Name: Úloha proteinu c-Myb v regulaci migrace, invazivity a apoptózy buněk střevního karcinomu (Acronym: c-Myb a invazivita CT26)
Investor: Masaryk University, Rector's Program