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

Název česky c-Myb reguluje MMP1/9 a cathepsin D - nový mechanismus matrix-dependentní invaze prsních nádorů
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KNOPFOVÁ Lucia BENEŠ Petr PEKARČÍKOVÁ Lucie HERMANOVÁ Markéta MASAŘÍK Michal ŠMARDA Jan

Rok publikování 2012
Druh Článek ve sborníku
Konference Cellular Signaling and Molecular Medicine
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
Obor Genetika a molekulární biologie
Klíčová slova myb breast carcinoma metastasis organotropism
Popis 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.
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