TY - JOUR
T1 - BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion
AU - Cekanova, Maria
AU - Fernando, Romaine I.
AU - Siriwardhana, Nalin
AU - Sukhthankar, Mugdha
AU - Parra, Columba de la
AU - Woraratphoka, Jirayus
AU - Malone, Christine
AU - Ström, Anders
AU - Baek, Seung J.
AU - Wade, Paul A.
AU - Saxton, Arnold M.
AU - Donnell, Robert M.
AU - Pestell, Richard G.
AU - Dharmawardhane, Suranganie
AU - Wimalasena, Jay
N1 - Funding Information:
This work was supported partially by NIH , USA Grant ( R01CA84048 , PI: Wimalasena), and two grants by the University of Tennessee Graduate School of Medicine Physician׳s Medical Education and Research Foundation ( R084025002 , PI: Wimalasena, and R181721242 , PI: Cekanova). Dr. Jay Wimalasena is thankful to undergraduate students of UT: Erica Smith, Rhett Layman, and Blair Tatge for their technical assistance.
Publisher Copyright:
© 2014 Elsevier Inc.
PY - 2015/2/1
Y1 - 2015/2/1
N2 - 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.
AB - 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.
KW - BAD
KW - Breast cancer
KW - Extracellular matrix invasion
KW - Metastasis
UR - http://www.scopus.com/inward/record.url?scp=84921310836&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2014.11.016
DO - 10.1016/j.yexcr.2014.11.016
M3 - Article
C2 - 25499972
AN - SCOPUS:84921310836
SN - 0014-4827
VL - 331
SP - 1
EP - 10
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 1
ER -
