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

BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion.
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DOI:
10.1016/j.yexcr.2014.11.016
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发表时间:
2015-02-01
影响因子:
3.7
通讯作者:
Wimalasena, Jay
Wimalasena, Jay
中科院分区:
医学3区
文献类型:
--
作者:
Cekartova, Maria;Fernando, Romaine I.;Siriwardhana, Nalin;Sukhthankar, Mugdha;de la Parra, Columba;Woraratphoka, Jirayus;Malone, Christine;Stroem, Anders;Baekd, Seung J.;Wadef, Paul A.;Saxton, Arnold M.;Donnell, Robert M.;Pestell, Richard G.;Dharmawardhane, Suranganie;Wimalasena, Jay

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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 were regulated by BAD with concomitant inhibition of extracellular matrix invasion. siRNA knockdown of BAD 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.
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