BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion
Authors: Anders Ström
Columba de la Parra
Arnold M Saxton
Jirayus Woraratphoka
Richard G Pestell
Jay Wimalasena
Seung J Baek
Nalin Siriwardhana
Robert M Donnell
Mugdha Sukhthankar
Suranganie Dharmawardhane
Romaine I Fernando
Paul A Wade
Maria Cekanova
Christine Malone
Journal: Experimental Cell Research (2015)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: BAD; Breast cancer; Extracellular matrix invasion; Metastasis.
Affiliations: Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN, USA. Electronic address: ., Department of Obstetrics and Gynecology, Graduate School of Medicine, Medical Center, The University of Tennessee, Knoxville, TN, USA., Department of Animal Science, The University of Tennessee, Knoxville, TN, USA., Department of Biomedical and Diagnostics Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN, USA., Department of Biochemistry, School of Medicine, University of Puerto Rico, Medical Sciences Campus, San Juan, PR, USA., Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA., Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX, USA., Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA., Department of Obstetrics and Gynecology, Graduate School of Medicine, Medical Center, The University of Tennessee, Knoxville, TN, USA. Electronic address: .

Abstract:  We have previously demonstrated that the anti-apoptotic protein BAD is expressed in normal human breast tissue and shown that BAD inhibits expression of cyclin D1 to delay cell-cycle progression in breast cancer cells. Herein, expression of proteins in breast tissues was studied by immunohistochemistry and results were analyzed statistically to obtain semi-quantitative data. Biochemical and functional changes in BAD-overexpressing MCF7 breast cancer cells were evaluated using PCR, reporter assays, western blotting, ELISA and extracellular matrix invasion assays. Compared to normal tissues, Grade II breast cancers expressed low total/phosphorylated forms of BAD in both cytoplasmic and nuclear compartments. BAD overexpression decreased the expression of β-catenin, Sp1, and phosphorylation of STATs. BAD inhibited Ras/MEK/ERK and JNK signaling pathways, without affecting the p38 signaling pathway. Expression of the metastasis-related proteins, MMP10, VEGF, SNAIL, CXCR4, E-cadherin and TlMP2 was regulated by BAD with concomitant inhibition of extracellular matrix invasion. Inhibition of BAD by siRNA increased invasion and Akt/p-Akt levels. Clinical data and the results herein suggest that in addition to the effect on apoptosis, BAD conveys anti-metastatic effects and is a valuable prognostic marker in breast cancer. 

Retracted: No

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 Figure 3A has a vertical mark that may indicate a splice. Shown below in inverse. Would the authors kindly supply an original uncropped scan? *** ![file] ,