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alpha-actinin-4, originally identified as an actin-binding protein associated with cell motility, invasion, and metastasis of cancer cells, appears to be overexpressed in various human epithelial carcinomas, including colorectal, breast, esophageal, ovarian, and non-small cell lung carcinomas. The authors evaluated whether alpha-actinin-4 might be appropriate as a molecular target for cancer gene therapy. In 64 primary oral squamous cell carcinomas (OSCCs) and 10 normal oral mucosal specimens, and in seven human OSCC cell lines, alpha-actinin-4 expression was evaluated immunologically and correlations with clinicopathologic factors were examined. Overexpression of alpha-actinin-4 was detected in 38 of 64 oral squamous cell carcinomas (70%); significantly more frequently than in normal oral mucosa. The expression of alpha-actinin-4 was significantly associated with invasion potential defined by the Matrigel invasion assay. Cancer cell lines with higher alpha-actinin-4 expression had greater invasive potential. An RNAi-mediated decrease in alpha-actinin-4 expression reduced the invasion potential. These results indicated that the overexpression of alpha-actinin-4 was associated with an aggressive phenotype of OSCC. The study indicated that alpha-actinin-4 could be a potential molecular target for gene therapy by RNAi targeting for OSCC., (Copyright 2009 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

The p53R2 gene encodes the ribonucleotide reductase (RR) small subunit 2 homologue, and is induced by several stress signals activating p53, such as DNA-damaging agents. The p53R2 gene product causes an increase in the deoxynucleotide triphosphate (dNTP) pool in the nucleus, which facilitates DNA repair and synthesis. We hypothesized that p53R2 would be a good molecular target for cancer gene therapy. In this study, three human oral cancer cell lines (SAS, HSC-4 and Ca9-22), a human breast cancer cell line MCF-7, and a normal human fibroblast cell line NHDF were tested. We silenced the expression of p53R2 with the highly specific post-transcriptional suppression of RNA interference (RNAi). We investigated p53R2 expression with the reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. The sensitivity to anticancer agents was evaluated by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of p53R2 showed no association with the mutational status of p53. The cancer cell lines with higher p53R2 expression were more resistant to 5-FU. RNAi-mediated p53R2 reduction selectivity inhibited growth and enhanced chemosensitivity in cancer cell lines but not in normal fibroblasts. These results suggest that basal transcription of p53R2 could be associated with the sensitivity to anticancer agents. Moreover, we assessed the possibility that p53R2 would be a good molecular target, and report that RNAi targeting of p53R2 could be useful for oral cancer gene therapy.

Abstract: α-actinin-4, originally identified as an actin-binding protein associated with cell motility, invasion, and metastasis of cancer cells, appears to be overexpressed in various human epithelial carcinomas, including colorectal, breast, esophageal, ovarian, and non-small cell lung carcinomas. The authors evaluated whether α-actinin-4 might be appropriate as a molecular target for cancer gene therapy. In 64 primary oral squamous cell carcinomas (OSCCs) and 10 normal oral mucosal specimens, and in seven human OSCC cell lines, α-actinin-4 expression was evaluated immunologically and correlations with clinicopathologic factors were examined. Overexpression of α-actinin-4 was detected in 38 of 64 oral squamous cell carcinomas (70%); significantly more frequently than in normal oral mucosa. The expression of α-actinin-4 was significantly associated with invasion potential defined by the Matrigel invasion assay. Cancer cell lines with higher α-actinin-4 expression had greater invasive potential. An RNAi-mediated decrease in α-actinin-4 expression reduced the invasion potential. These results indicated that the overexpression of α-actinin-4 was associated with an aggressive phenotype of OSCC. The study indicated that α-actinin-4 could be a potential molecular target for gene therapy by RNAi targeting for OSCC. [Copyright &y& Elsevier]

Abstract: Metastasis-associated protein 1 (MTA1) is physiologically expressed at low levels in human tissues. Its expression is associated with progression of solid cancers and is common in cancer cell lines. This study investigated whether MTA1 was expressed in squamous cell carcinoma (SCC) and would be a useful metastatic marker. Specimens from 38 patients with oral SCC were stained using the avidin-biotin-peroxidase technique with polyclonal antibodies against MTA1. Human SCC cell lines SAS, HSC2, OSC19 and OSC20 were analysed for MTA1 mRNA expression. MTA1 expression in control tissues was significantly lower than in carcinomas. MTA1 protein expression was detected in 33 of 38 SCC tissues from patients. Histologically, MTA1 protein production was strongly associated with cancer cell invasion, and clinically there was a correlation between lymph node metastasis and MTA1 protein production. Among the cancer cell lines, HSC2 showed the lowest mRNA expression, and OSC20 showed the highest MTA1 mRNA expression. In the Matrigel invasion assay, the HSC2 cell line showed the lowest invasion and the OSC20 cell line showed the highest invasion. RNAi-mediated MTA1 silencing in the OSC20 cells decreased the invasion index. MTA1 expression in oral SCC may be associated with increased invasive ability, which may cause lymph node metastasis. [Copyright &y& Elsevier]