A Histone Deacetylase Inhibitor Enhances Adenoviral Infection of Renal Cancer Cells

Okegawa, Takatsugu; Sayne, Jennifer R.; Nutahara, Kikuo; Pong, Rey-Chen; Saboorian, Hossain; Kabbani, Wareef; Higashihara, Eiji; Hsieh, Jer Tsong

doi:10.1016/j.juro.2006.10.034

Cited by 14 publications

(16 citation statements)

References 13 publications

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“…These findings led to the hypothesis of a tumour suppressive role for CAR in human cancers. In line with this hypothesis, reduced presence of CAR was found in advanced cancers in part associated with loss of tumour differentiation, increased infiltration, and a poor prognosis Sachs et al, 2002;Matsumoto et al, 2005;Korn et al, 2006;Buscarini et al, 2007;Okegawa et al, 2007). In gastric adenocarcinomas, an immunohistochemical analysis of cancer tissues from 30 patients and 11 non-cancerous controls showed reduced CAR staining intensities in gastric cancer (Heideman et al, 2001).…”

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confidence: 64%

Loss of the coxsackie and adenovirus receptor contributes to gastric cancer progression

et al. 2009

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Loss of the coxsackie and adenovirus receptor (CAR) has previously been observed in gastric cancer. The role of CAR in gastric cancer pathobiology, however, is unclear. We therefore analysed CAR in 196 R 0 -resected gastric adenocarcinomas and noncancerous gastric mucosa samples using immunohistochemistry and immunofluorescence. Coxsackie and adenovirus receptor was found at the surface and foveolar epithelium of all non-neoplastic gastric mucosa samples (n ¼ 175), whereas only 56% of gastric cancer specimens showed CAR positivity (Po0.0001). Loss of CAR correlated significantly with decreased differentiation, increased infiltrative depths, presence of distant metastases, and was also associated with reduced carcinoma-specific survival. To clarify whether CAR impacts the tumorbiologic properties of gastric cancer, we subsequently determined the role of CAR in proliferation, migration, and invasion of gastric cancer cell lines by application of specific CAR siRNA or ectopic expression of a human full-length CAR cDNA. These experiments showed that RNAi-mediated CAR knock down resulted in increased proliferation, migration, and invasion of gastric cancer cell lines, whereas enforced ectopic CAR expression led to opposite effects. We conclude that the association of reduced presence of CAR in more severe disease states, together with our findings in gastric cancer cell lines, suggests that CAR functionally contributes to gastric cancer pathogenesis, showing features of a tumour suppressor.

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confidence: 64%

Loss of the coxsackie and adenovirus receptor contributes to gastric cancer progression

et al. 2009

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“…In several human carcinomas, particularly in more advanced stages, a reduced CAR presence was found, partially associated with loss of tumour differentiation, increased infiltration, and poor prognosis (Sachs et al, 2002;Matsumoto et al, 2005;Korn et al, 2006;Buscarini et al, 2007;Okegawa et al, 2007;Anders et al, 2009). On the basis of data from studies in cell lines, it has been speculated that loss of CAR promotes the proliferation, migration, and invasion of cancer cells (Okegawa et al, 2000(Okegawa et al, , 2001Runnebaum, 2003, 2004;Huang et al, 2005;Wang et al, 2005).…”

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confidence: 99%

Loss of Coxsackie and adenovirus receptor downregulates α-catenin expression

et al. 2009

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BACKGROUND: The Coxsackie and adenovirus receptor (CAR) has been shown to inhibit cancer cell proliferation, migration, and invasion. The underlying mechanisms, however, are poorly understood. METHODS: The differential gene expression in the human colon cancer cell line DLD1 on RNAi-mediated functional CAR knockdown was analysed using oligo-array technology. Expression of a-catenin was determined by quantitative RT-PCR and western blotting. Proliferation, migration, and invasion after CAR knockdown were assessed by in vitro assays, and cell morphology in a threedimensional context was evaluated using matrigel. RESULTS: Oligo-array technology identified a-catenin as the strongest downregulated gene after CAR knockdown. Western blotting and quantitative RT-PCR confirmed a reduced a-catenin expression after CAR knockdown in DLD1 cells and in the rat intestinal cell line IEC-6. Functionally, both cell lines showed a marked increase in proliferation, migration, and invasion on CAR knockdown. In matrigel, both cell lines formed amorphous cell clusters in contrast to well-organised three-dimensional structures of CAR-expressing vector controls. Ectopic 're'-expression of a-catenin in DLD1 and IEC-6 CAR knockdown cells reversed these functional and morphological effects. CONCLUSION: These data suggest that an interaction of CAR and a-catenin mediates the impact of CAR on cell proliferation, migration, invasion, and morphology.

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“…To date, the role of CAR in breast cancer and the factors regulating CAR expression are poorly understood. Previous studies have shown that treatment of cancer cells with histone deacetylase inhibitors upregulates CAR expression (Kitazono et al 2001, Hemminki et al 2003, Pong et al 2003, Okegawa et al 2007. Other signals such as the MAPK pathway, the action of glucocorticoids, tumour necrosis factor a, and transforming growth factor-b also modulate CAR expression (Anders et al 2003, Bruning & Runnebaum 2003.…”

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confidence: 99%

Coxsackie and adenovirus receptor is a target and a mediator of estrogen action in breast cancer

Vindrieux¹,

Corre²,

Hsieh³

et al. 2011

Endocrine-Related Cancer

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The involvement of the coxsackie and adenovirus receptor (CAR), an adhesion molecule known to be the main determinant of adenovirus transduction of the cells, in cancer is currently under investigation. Recent reports suggest that CAR levels are elevated in breast cancer, and this may have an impact on its use as means of delivery for gene therapy. In this study, we show that estradiol (E 2 ) treatment of the estrogen receptor (ER)-positive breast cancer cell MCF-7 increases CAR levels and, in turn, enhances adenoviral transduction. Employing the transfection of CAR promoters in breast cancer cells, we show that this regulation of CAR expression occurs at the transcriptional level. In addition, and by chromatin immunoprecipitation, we have identified a crucial region of CAR promoter that controls E 2 responsiveness of CAR gene through the recruitment of ER. Moreover, utilizing CAR antibodies or CAR silencing by RNA interference repressed the estrogen-dependent growth of breast cancer cells, whereas the stable expression of CAR in MCF-7 or MDA-MB-231 cells led to an increased proliferation. Altogether, our data suggest that CAR is a novel estrogen-responsive gene, which is involved in the E 2 -dependent proliferation of breast cancer cells.

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A Histone Deacetylase Inhibitor Enhances Adenoviral Infection of Renal Cancer Cells

Abstract: In human renal cancer specimens a loss of or decrease in coxsackie and adenovirus receptor expression may be an early event in renal cancer progression. Pretreatment with FK-228 may increase tumor cell sensitivity to adenoviral gene therapy vectors.

Cited by 14 publications

References 13 publications

Loss of the coxsackie and adenovirus receptor contributes to gastric cancer progression

Loss of the coxsackie and adenovirus receptor contributes to gastric cancer progression

Loss of Coxsackie and adenovirus receptor downregulates α-catenin expression

Coxsackie and adenovirus receptor is a target and a mediator of estrogen action in breast cancer

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