BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion
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. - Highlights: • BAD and p-BAD expressions are decreased in breast cancer compared with normal breast tissue.more »
- Authors:
-
- Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN (United States)
- Department of Obstetrics and Gynecology, Graduate School of Medicine, Medical Center, The University of Tennessee, Knoxville, TN (United States)
- Department of Animal Science, The University of Tennessee, Knoxville, TN (United States)
- Department of Biomedical and Diagnostics Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN (United States)
- Department of Biochemistry, School of Medicine, University of Puerto Rico, Medical Sciences Campus, San Juan, PR (United States)
- Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States)
- Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX (United States)
- Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States)
- Publication Date:
- OSTI Identifier:
- 22462249
- Resource Type:
- Journal Article
- Journal Name:
- Experimental Cell Research
- Additional Journal Information:
- Journal Volume: 331; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; APOPTOSIS; BORON CHLORIDES; CHEMILUMINESCENCE; DEATH; ENZYME IMMUNOASSAY; ESTROGENS; FLUORESCENCE; GLYCOGEN; GROWTH FACTORS; LYMPHOMAS; MAMMARY GLANDS; METASTASES; MYELOID LEUKEMIA; PEROXIDASES; PHOSPHATES; PHOSPHORUS 38; PHOSPHOTRANSFERASES; POLYMERASE CHAIN REACTION; RECEPTORS; SIGNALS; SNAILS; TRANSCRIPTION; TRANSCRIPTION FACTORS
Citation Formats
Cekanova, Maria, Fernando, Romaine I., Siriwardhana, Nalin, Sukhthankar, Mugdha, Parra, Columba de la, Woraratphoka, Jirayus, Malone, Christine, Ström, Anders, Baek, Seung J., Wade, Paul A., Saxton, Arnold M., Donnell, Robert M., Pestell, Richard G., and others, and. BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion. United States: N. p., 2015.
Web. doi:10.1016/J.YEXCR.2014.11.016.
Cekanova, Maria, Fernando, Romaine I., Siriwardhana, Nalin, Sukhthankar, Mugdha, Parra, Columba de la, Woraratphoka, Jirayus, Malone, Christine, Ström, Anders, Baek, Seung J., Wade, Paul A., Saxton, Arnold M., Donnell, Robert M., Pestell, Richard G., & others, and. BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion. United States. https://doi.org/10.1016/J.YEXCR.2014.11.016
Cekanova, Maria, Fernando, Romaine I., Siriwardhana, Nalin, Sukhthankar, Mugdha, Parra, Columba de la, Woraratphoka, Jirayus, Malone, Christine, Ström, Anders, Baek, Seung J., Wade, Paul A., Saxton, Arnold M., Donnell, Robert M., Pestell, Richard G., and others, and. 2015.
"BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion". United States. https://doi.org/10.1016/J.YEXCR.2014.11.016.
@article{osti_22462249,
title = {BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion},
author = {Cekanova, Maria and Fernando, Romaine I. and Siriwardhana, Nalin and Sukhthankar, Mugdha and Parra, Columba de la and Woraratphoka, Jirayus and Malone, Christine and Ström, Anders and Baek, Seung J. and Wade, Paul A. and Saxton, Arnold M. and Donnell, Robert M. and Pestell, Richard G. and others, and},
abstractNote = {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. - Highlights: • BAD and p-BAD expressions are decreased in breast cancer compared with normal breast tissue. • BAD impedes breast cancer invasion and migration. • BAD inhibits the EMT and transcription factors that promote cancer cell migration. • Invasion and migration functions of BAD are distinct from the BAD's role in apoptosis.},
doi = {10.1016/J.YEXCR.2014.11.016},
url = {https://www.osti.gov/biblio/22462249},
journal = {Experimental Cell Research},
issn = {0014-4827},
number = 1,
volume = 331,
place = {United States},
year = {Sun Feb 01 00:00:00 EST 2015},
month = {Sun Feb 01 00:00:00 EST 2015}
}