Silencing of the p53R2 gene by RNA interference inhibits growth and enhances 5-fluorouracil sensitivity of oral cancer cells

Yanamoto, Souichi; Iwamoto, Tsutomu; Kawasaki, Goro; Yoshitomi, Izumi; Baba, Naomichi; Mizuno, Akio

doi:10.1016/j.canlet.2004.10.019

Cited by 39 publications

(23 citation statements)

References 19 publications

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“…RNAi technology is a specific and powerful tool to turn off the expression of oncogenic target genes [74]. In oral cancers, the possibility of RNA-mediated gene therapy has been reported 75,76]. We successfully applied double RNA silencing to inhibit the expression of cortactin and CRKII, and thereby decreased the invasive potential of OSCC.…”

Section: Discussionmentioning

confidence: 99%

Co-overexpression of cortactin and CRKII increases migration and invasive potential in oral squamous cell carcinoma

Yamada

Yanamoto

Rokutanda

et al. 2014

Journal of Oral and Maxillofacial Surgery, Medicine, and Pathol

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Cortactin stimulates cell migration, invasion, and experimental metastasis. Overexpression of cortactin has been reported in several human cancers. CRK was originally identified as an oncogene product of v-CRK in a CT10 chicken retrovirus system. Overexpression of CRKII has been reported in several human cancers. CRKII regulates cell migration, morphogenesis, invasion, phagocytosis, and survival; however, the underlying mechanisms are not well understood. We evaluated the possibility of the combination of cortactin and CRKII as an appropriate molecular target for cancer gene therapy. The expression of cortactin and CRKII in 70 primary oral squamous cell carcinomas and 10 normal oral mucosal specimens was determined immunohistochemically, and the correlation of cortactin and CRKII co-overexpression with clinicopathological factors was evaluated. Co-overexpression of cortactin and CRKII was detected in 31 of 70 oral squamous cell carcinomas, the frequency being significantly greater than in normal oral mucosa. In addition, cortactin and CRKII co-overexpression was more frequent in higher-grade cancers according to 3 the T classification, N classification, and invasive pattern. RNAi-mediated co-suppression of cortactin and CRKII expression reduced the migration and invasion potential of an oral squamous cell carcinoma cell line, OSC20. Downregulation of cortactin and CRKII expression also reduced the expression of vimentin, fibronectin, and N-cadherin. These results indicate that the co-overexpression of cortactin and CRKII may be tightly associated with an aggressive phenotype of oral squamous cell carcinoma. Therefore, we propose that the combination of cortactin and CRKII could be a potential molecular target of gene therapy by RNAi-targeting in oral squamous cell carcinoma. 4 1.IntroductionOral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck region and accounts for more than 90% of cancers of the oral cavity [1]. The primary therapeutic modality for OSCC is surgery. Although recent advances in surgical techniques and anticancer agents have improved tumor regression and survival for patients with OSCC, wide surgical resection of OSCC inevitably causes various oral dysfunctions. Therefore, new treatment strategies are urgently needed.The presence of neck lymph node metastasis is strongly related to a poor prognosis in squamous cell carcinoma of the head and neck [2][3][4]. Moreover, it has been reported that an alteration in the expression of adhesion-related molecules is associated with poor prognosis in OSCC patients [5][6][7][8].Chromosomal band 11q13 is a frequently amplified genomic segment in a large number of malignant neoplasms, and is thought of as a potential biomarker for diagnosis and prognosis [9,10]. In head and neck squamous cell carcinoma, this amplification is one of the most frequently observed genetic alterations [11][12][13][14][15][16][17][18][19][20] and is reportedly correlated with aggressive tumor growth [9,13,19], the presence of lymph node ...

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Section: Discussionmentioning

confidence: 99%

Co-overexpression of cortactin and CRKII increases migration and invasive potential in oral squamous cell carcinoma

Yamada

Yanamoto

Rokutanda

et al. 2014

Journal of Oral and Maxillofacial Surgery, Medicine, and Pathol

Self Cite

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“…In oral cancers, the possibility of RNA-mediated gene therapy has been reported [57,58]. We successfully applied RNA silencing to inhibit the expression of CRKII, and thereby decreased the invasive potential of OSCC.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of CRKII increases migration and invasive potential in oral squamous cell carcinoma

et al. 2011

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CT10 regulator of kinase (CRK) was originally identified as an oncogene product of v-CRK in a CT10 chicken retrovirus system. Overexpression of CRKII has been reported in several human cancers. CRKII regulates cell migration, morphogenesis, invasion, phagocytosis, and survival; however, the underlying mechanisms are not well understood. In the present study, we evaluated the possibility of CRKII as an appropriate molecular target for cancer gene therapy. The expression of CRKII in 71 primary oral squamous cell carcinomas and 10 normal oral mucosal specimens was determined immunohistochemically, and the correlation of CRKII overexpression with clinicopathological factors was evaluated.Overexpression of CRKII was detected in 41 of 70 oral squamous cell carcinomas, the frequency being more significant than in normal oral mucosa. In addition, CRKII overexpression was more frequent in higher-grade cancers according to the T classification, N classification, and invasive pattern. Moreover, RNAi-mediated suppression of CRKII expression reduced the migration and invasion potential of an oral squamous cell carcinoma cell line, OSC20. Downregulation of CRKII expression also reduced the expression of Dock180, p130Cas, and Rac1, and the actin-associated scaffolding protein cortactin. These results indicate that the overexpression of CRKII is tightly associated with an aggressive phenotype of oral squamous cell carcinoma. Therefore, we propose that CRKII could be a potential molecular target of gene therapy by RNAi-targeting in oral squamous cell carcinoma. 4

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“…29) In previous studies, normal human dermal fibroblasts (NHDF) and peripheral blood mononuclear cells (PBMC) have also been used as control normal cells to clarify tumor selectivity. [30][31][32] We also examined chalcone-induced cytotoxicity using NHDF cells, but all of the chalcones (1-8) showed cytotoxic effects against NHDF, as well as neuroblastoma cells, by MTT assay (data not shown). From these results, it seems difficult to explain the tumor selectivity solely by comparing a few types of normal cells in vitro.…”

Section: Discussionmentioning

confidence: 99%

Isobavachalcone, a Chalcone Constituent of Angelica keiskei, Induces Apoptosis in Neuroblastoma

Nishimura

Tabata

Arakawa

et al. 2007

Biological & Pharmaceutical Bulletin

139

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Six chalcones from Angelica keiskei KOIDZUMI (Ashitaba in Japanese) and two chalcones from Humulus lupulus L. (hop) were examined for their cytotoxicity in two human neuroblastoma cell lines (IMR-32 and NB-39) and normal cells (primary culture of rat cerebellar granule cells) by [3-(4,5)-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. All chalcones exhibited cytotoxicity against neuroblastoma cells, and two of them (isobavachalcone and xanthoangelol H) had no effect on normal cells even at high concentration (10 ؊4 M) exposure. Typical morphologic features of apoptosis, including cell shrinkage, chromatin condensation, nuclear fragmentation and formation of apoptotic bodies, were observed in isobavachalcone-treated cells by Hoechst 33342 staining. Western blot analysis showed that isobavachalcone significantly reduced pro-caspase-3 and pro-caspase-9, and subsequently increased the level of cleaved caspase-3 and cleaved caspase-9 in both neuroblastoma cell lines. Moreover, Bax was markedly induced by isobavachalcone application. These results suggest that isobavachalcone induces apoptotic cell death in neuroblastoma via the mitochondrial pathway and has no cytotoxicity against normal cells. Therefore, isobavachalcone may be applicable as an efficacious and safe drug for the treatment of neuroblastoma.

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Silencing of the p53R2 gene by RNA interference inhibits growth and enhances 5-fluorouracil sensitivity of oral cancer cells

Cited by 39 publications

References 19 publications

Co-overexpression of cortactin and CRKII increases migration and invasive potential in oral squamous cell carcinoma

Co-overexpression of cortactin and CRKII increases migration and invasive potential in oral squamous cell carcinoma

Overexpression of CRKII increases migration and invasive potential in oral squamous cell carcinoma

Isobavachalcone, a Chalcone Constituent of Angelica keiskei, Induces Apoptosis in Neuroblastoma

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