Mammaglobin 1 promotes breast cancer malignancy and confers sensitivity to anticancer drugs

Abstract

Mammaglobin 1 (MGB1), a member of the secretoglobin family, is expressed in mammary epithelial tissues and is overexpressed in most mammary carcinomas. Despite the extensive research correlating MGB1 expression profiles to breast cancer pathogenesis and disease outcome, the biological significance of MGB1 in cancer processes is still unclear. We have thus set out to conduct a functional evaluation of the molecular and cellular roles of MGB1 in breast cancer processes leading to disease progression. Using a series of breast cancer cell models with conditional MGB1 expression, we demonstrate that MGB1 promotes cancer cell malignant features. More specifically, loss of MGB1 expression resulted in a decrease of cell proliferation, soft agar spheroid formation, migration, and invasion capacities of breast cancer cells. Concomitantly, we also observed that MGB1 expression activates signaling pathways mediated by MAPK members (p38, JNK, and ERK), the focal adhesion kinase (FAK), matrix metalloproteinases (MMPs) and NFκB. Moreover, MGB1 regulates epithelial to mesenchymal (EMT) features and modulates Snail, Twist and ZEB1 expression levels. Interestingly, we also observed that expression of MGB1 confers breast cancer cell sensitivity to anticancer drug-induced apoptosis. Together, our results support a role for MGB1 in tumor malignancy in exchange for chemosensitivity. These findings provide one of the first descriptive overview of the molecular and cellular roles of MGB1 in breast cancer processes and may offer new insight to the development of therapeutic and prognostic strategies in breast cancer patients. © 2015 Wiley Periodicals, Inc.

Microvessel Density and Mammaglobin A Expression as Prognostic Markers in Molecular Types of Breast Cancer

“…Our findings suggest the possibility of an inversely proportional relation between MVD and MGB in a limited number of breast cancer specimens. The cases in which we identified a strong MGB expression and increased MVD values, may partially support the findings of Picot et al regarding MGB-A implications in promoting cancer cell malignant features [34]. The authors of this study demonstrated that the loss of MGB-A expression determines a decrease of tumor cell proliferation [34].…”

“…The cases in which we identified a strong MGB expression and increased MVD values, may partially support the findings of Picot et al regarding MGB-A implications in promoting cancer cell malignant features [34]. The authors of this study demonstrated that the loss of MGB-A expression determines a decrease of tumor cell proliferation [34]. However, these results need to be further investigated in order to become applicable in daily clinical practice.…”

“…MGB-A implications as a prognostic parameter in breast cancer patients remain controversial at the time being. The studies conducted in the field of breast cancer either support its negligible role compared to other biomarkers [30,42] or are in favor of MGB-A implications in cancer cell proliferation and poor patient outcome [34]. Despite the available data, MGB may not be as completely elucidated as it seems at the time being.…”

Pax-5 is a potent regulator of E-cadherin and breast cancer malignant processes

“…Levels of gene expression were verified by quantitative real-time RT-PCR (RT-qPCR) as previously described [46] using specific PCR primer pairs (Supplementary Table 3). Comparative expression levels were calculated using the ΔΔCt method of Livak and Schmittgen, (2001) [47], using the hypoxanthine ribosyltransferase (HPRT) transcript as a normalizing control.…”

Pax-5 Inhibits Breast Cancer Proliferation Through MiR-215 Up-regulation

“…Cell viability assays. Cellular viability was monitored using the CellTiter-Blue assay (Promega, Madison, WI, USA) as previously described (29). After transfection, cells were seeded in 96 well plates (3×10 3 cells/well) where 20 μl of CellTiter-Blue substrate was added up to 100 μl/well and incubated for 1 h at 37˚C.…”