BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion

Maria Cekanova, Romaine I. Fernando, Nalin Siriwardhana, Mugdha Sukhthankar, Columba de la Parra, Jirayus Woraratphoka, Christine Malone, Anders Ström, Seung J. Baek, Paul A. Wade, Arnold M. Saxton, Robert M. Donnell, Richard G. Pestell, Suranganie Dharmawardhane, Jay Wimalasena

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalExperimental Cell Research
Volume331
Issue number1
DOIs
Publication statusPublished - 1 Feb 2015
Externally publishedYes

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