Journal Article

VAMP-Associated Protein B (VAPB) Promotes Breast Tumor Growth by Modulation of Akt Activity

Shyr, Yu, Rao, Meghana, Song, Wenqiang, Jiang, Aixiang, Chen, Jin, Greenstein, David, Lev, Sima, Brantley-Sieders, Dana

2012

Overview

VAPB (VAMP- associated protein B) is an ER protein that regulates multiple biological functions. Although aberrant expression of VAPB is associated with breast cancer, its function in tumor cells is poorly understood. In this report, we provide evidence that VAPB regulates breast tumor cell proliferation and AKT activation. VAPB protein expression is elevated in primary and metastatic tumor specimens, and VAPB mRNA expression levels correlated negatively with patient survival in two large breast tumor datasets. Overexpression of VAPB in mammary epithelial cells increased cell growth, whereas VAPB knockdown in tumor cells inhibited cell proliferation in vitro and suppressed tumor growth in orthotopic mammary gland allografts. The growth regulation of mammary tumor cells controlled by VAPB appears to be mediated, at least in part, by modulation of AKT activity. Overexpression of VAPB in MCF10A-HER2 cells enhances phosphorylation of AKT. In contrast, knockdown of VAPB in MMTV-Neu tumor cells inhibited pAKT levels. Pharmacological inhibition of AKT significantly reduced three-dimensional spheroid growth induced by VAPB. Collectively, the genetic, functional and mechanistic analyses suggest a role of VAPB in tumor promotion in human breast cancer.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Aberration / AKT protein / Allografts / Amyotrophic lateral sclerosis / Analysis / Analysis of Variance / Animals / Apoptosis / Binding sites / Biology / Breast cancer / Breast Neoplasms - metabolism / Breast Neoplasms - physiopathology / Cancer / Cancer metastasis / Cancer treatment / Cell activation / Cell growth / Cell Line, Tumor / Cell Proliferation / Datasets / Endoplasmic reticulum / Enzyme Activation - physiology / Epithelial cells / ErbB-2 protein / Female / Gene expression / Gene Expression Profiling / Genomes / Growth / Growth factors / Humans / Immunoblotting / Immunohistochemistry / Inhibition / Kinases / Ligands / Lipids / Mammary gland / Medicine / Metastases / Mice / Microarray Analysis / Modulation / Mutation / Oncogene Protein v-akt - metabolism / Pharmacology / Phosphorylation / Physicians / Plasmids / Plasmids - genetics / Protein B / Proteins / RNA / Rodents / Spheroids, Cellular - cytology / Survival Analysis / Tumor cells / Tumors / Vesicular Transport Proteins - metabolism / Virulence-associated protein B