Publication details

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

Authors

KNOPFOVÁ Lucia BENEŠ Petr PEKARČÍKOVÁ Lucie HERMANOVÁ Markéta MASAŘÍK Michal ŠMARDA Jan

Type Article in Proceedings
Conference Cellular Signaling and Molecular Medicine
MU Faculty or unit

Faculty of Science

Citation
Field Genetics and molecular biology
Keywords myb breast carcinoma metastasis organotropism
Description 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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