REIC/Dkk-3 as a potential gene therapeutic agent against human testicular cancer

Tanimoto, Ryuta; Abarzúa, Fernando; Sakaguchi, Masakiyo; Takaishi, Mikiro; Nasu, Yasutomo; Kumon, Hiromi; Huh, Nam

doi:10.3892/ijmm.19.3.363

Cited by 49 publications

(88 citation statements)

References 19 publications

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“…1,2,5 In prostate cancer PC-3 cells, the overexpression of REIC/Dkk-3 activates JNK, reduces the Bcl-2 protein level, induces the mitochondrial translocation of Bax protein, releases cytochrome c into the cytoplasm, thus finally leading to apoptotic cell death. 1 This study first demonstrated that cleaved caspase-3 was involved in the Ad-REIC-induced apoptotic pathway.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5][6][7][8] The REIC gene is identical to Dickkopf-3 (Dkk-3) gene and REIC/Dkk-3 has been considered as a tumor suppressor gene to provide a new means of gene therapy for some of the human malignant tumors. The forced expression of REIC/Dkk-3, using a plasmid vector, inhibited cell growth in HeLa and liver cancer cell lines.…”

Section: Introductionmentioning

confidence: 99%

“…9 Adenovirus vector carrying REIC/Dkk-3 selectively induced apoptosis in prostate cancer and testicular cancer cells through the activation of c-Jun-NH 2 -kinase (JNK) and c-Jun. 1,5 Breast cancer is one of the most common female malignancies in the world. Although a definite therapeutic effect has been achieved by existing treatment modalities of surgery, hormonal therapy, chemotherapy and radiation, a considerable number of patients experience disease progression and recurrence.…”

Section: Introductionmentioning

confidence: 99%

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REIC/Dkk-3 overexpression downregulates P-glycoprotein in multidrug-resistant MCF7/ADR cells and induces apoptosis in breast cancer

et al. 2008

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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REIC/Dkk-3 overexpression downregulates P-glycoprotein in multidrug-resistant MCF7/ADR cells and induces apoptosis in breast cancer

et al. 2008

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“…The REIC/Dkk-3 protein is ubiquitously expressed in mouse and human organs and in normal cells, but its expression is significantly downregulated in a variety of cancer cells [2]. Several investigators have previously demonstrated that overexpression of REIC/Dkk-3 induces apoptosis in multiple cancer cell lines [3][4][5][6]. The forced expression of REIC/Dkk-3 using a plasmid vector inhibited cell growth in HeLa and liver cancer cell lines [3].…”

Section: Reic (Reduced Expression In Immortalized Cells) Is a Tumor Smentioning

confidence: 99%

Tumor suppressor REIC/Dkk-3 interacts with the dynein light chain, Tctex-1

Ochiai

Watanabe

Ueki

et al. 2011

Biochemical and Biophysical Research Communications

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“…REIC/Dkk-3 expression is down-regulated in a broad range of cancer cell lines and clinical cancer materials (2)(3)(4)(5)(6)(7)(8)(9)(10). The expression of the human REIC/Dkk-3 gene is significantly down-regulated in human prostate cancer specimens in comparison to normal human prostate tissue at the protein level (5).…”

Section: Introductionmentioning

confidence: 99%

REIC/Dkk-3 stable transfection reduces the malignant phenotype of mouse prostate cancer RM9 cells

Chen

Watanabe²,

Huang³

et al. 2009

Int J Mol Med

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Abstract. The reduced expression in immortalized cells (REIC)/Dickkopf (Dkk)-3, a member of the Dkk gene family, is a tumor suppressor in a broad range of cancers. REIC/Dkk-3 transfected stable clones of mouse prostate cancer RM9 cells (RM9-REIC) and the empty vector-transfected control clone cells (RM9-EV) were established. Clones were used to evaluate the anti-cancer effects and a proteomics analysis of REIC/Dkk-3 continuous expression was performed. The RM9-REIC cells show a feeble appearance and the cell membrane shows irregular buds known as blebs. In vitro cell proliferation was significantly suppressed in RM9-REIC clones in comparison to the control. The apoptosis assay was done under standard culture conditions and RM9-REIC showed a higher incidence of apoptosis. The RM9-EV and RM9-REIC cells were orthotopically implanted into a C57BL/6 mouse prostate. After 2 weeks, the tumor growth was significantly inhibited in RM9-REIC cells in comparison to the control. Two-dimensional gel electrophoresis was used to examine the modification of protein expression by the gene transfection. The analysis with mass spectrometry disclosed that expression of peroxiredoxin-1, GST-P1, transgelin-2, MRP-L12, ARD, GRP78 and Sorcin were increased and eEF1A-1 and cyclophilin-40 protein were decreased in RM9-REIC cells. Therefore, REIC/Dkk-3 stable transfectants show a reduction of malignancy in mouse prostate cancer RM9 cells in vitro and in vivo. The result of the proteomics analysis might provide important clues to clarify the anti-cancer molecular mechanism of REIC/Dkk-3 gene transfer.

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REIC/Dkk-3 as a potential gene therapeutic agent against human testicular cancer

Cited by 49 publications

References 19 publications

REIC/Dkk-3 overexpression downregulates P-glycoprotein in multidrug-resistant MCF7/ADR cells and induces apoptosis in breast cancer

REIC/Dkk-3 overexpression downregulates P-glycoprotein in multidrug-resistant MCF7/ADR cells and induces apoptosis in breast cancer

Tumor suppressor REIC/Dkk-3 interacts with the dynein light chain, Tctex-1

REIC/Dkk-3 stable transfection reduces the malignant phenotype of mouse prostate cancer RM9 cells

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