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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-12-16
pubmed:abstractText
The overexpression of reduced expression in immortalized cells (REIC)/Dickkopf-3 (Dkk-3), a tumor suppressor gene, induced apoptosis in human prostatic and testicular cancer cells. The aim of this study is to examine the potential of REIC/Dkk-3 as a therapeutic target against breast cancer. First, the in vitro apoptotic effect of Ad-REIC treatment was investigated in breast cancer cell lines and the adenovirus-mediated overexpression of REIC/Dkk-3 was thus found to lead to apoptotic cell death in a c-Jun-NH(2)-kinase (JNK) phosphorylaion-dependent manner. Moreover, an in vivo apoptotic effect and MCF/Wt tumor growth inhibition were observed in the mouse model after intratumoral Ad-REIC injection. As multidrug resistance (MDR) is a major problem in the chemotherapy of progressive breast cancer, the in vitro effects of Ad-REIC treatment were investigated in terms of the sensitivity of multidrug-resistant MCF7/ADR cells to doxorubicin and of the P-glycoprotein expression. Ad-REIC treatment in MCF7/ADR cells also downregulated P-glycoprotein expresssion through JNK activation, and sensitized its drug resistance against doxorubicin. Therefore, not only apoptosis induction but also the reversal of anticancer drug resistance was achieved using Ad-REIC. We suggest that REIC/Dkk-3 is a novel target for breast cancer treatment and that Ad-REIC might be an attractive agent against drug-resistant cancer in combination with conventional antineoplastic agents.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1476-5500
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
65-72
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18654608-Adenoviridae, pubmed-meshheading:18654608-Animals, pubmed-meshheading:18654608-Antibiotics, Antineoplastic, pubmed-meshheading:18654608-Apoptosis, pubmed-meshheading:18654608-Breast Neoplasms, pubmed-meshheading:18654608-Down-Regulation, pubmed-meshheading:18654608-Doxorubicin, pubmed-meshheading:18654608-Drug Resistance, Multiple, pubmed-meshheading:18654608-Drug Resistance, Neoplasm, pubmed-meshheading:18654608-Enzyme Activation, pubmed-meshheading:18654608-Female, pubmed-meshheading:18654608-Gene Therapy, pubmed-meshheading:18654608-HeLa Cells, pubmed-meshheading:18654608-Humans, pubmed-meshheading:18654608-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:18654608-MAP Kinase Kinase 4, pubmed-meshheading:18654608-Mice, pubmed-meshheading:18654608-Mice, Nude, pubmed-meshheading:18654608-Neoplasm Transplantation, pubmed-meshheading:18654608-P-Glycoprotein
pubmed:year
2009
pubmed:articleTitle
REIC/Dkk-3 overexpression downregulates P-glycoprotein in multidrug-resistant MCF7/ADR cells and induces apoptosis in breast cancer.
pubmed:affiliation
Department of Cancer and Thoracic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't