Oral cancer and genetic polymorphism of DNA double strand break gene Ku70 in Taiwan

Bau, Da Tian; Tseng, Hsien Chang; Wang, Chung Hsing; Chiu, Chang Fang; Hua, Chun Hung; Wu, Cheng Nan; Liang, Shiu Yun; Wang, Cheng Li; Tsai, Chia Wen; Tsai, Ming Hsui

doi:10.1016/j.oraloncology.2008.02.008

Cited by 58 publications

(53 citation statements)

References 17 publications

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“…The SAS cell line (human oral squamous cell carcinoma) was obtained from Dr Pei-Jung Lu (Graduate Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan). Cells were cultured in DMEM containing 10% FBS, 2 mM L-glutamine, 100 U/ml penicillin and 100 µg/ml streptomycin in 75 cm 2 tissue culture flasks at 37˚C under a humidified 5% CO 2 and 95% air atmosphere. DAPI staining.…”

Section: Methodsmentioning

confidence: 99%

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Tetrandrine induces cell death in SAS human oral cancer cells through caspase activation-dependent apoptosis and LC3-I and LC3-II activation-dependent autophagy

Huang¹,

Lien

Meng

et al. 2013

International Journal of Oncology

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Abstract. Numerous studies have demonstrated that autophagy is associated with cancer development. Thus, agents to induce autophagy could be employed in some cases for the treatment of cancer. Our results showed that tetrandrine significantly decreased the viability of SAS cells in a concentration-and time-dependent manner. Tetrandrine induced nuclear condensation, demonstrated by DAPI staining. The early events in apoptosis analysed by Annexin V/PI staining indicated that the percentage of cells staining positive for Annexin V was slightly increased in SAS cells with tetrandrine treatment but was much lower following bafilomycin A1 pre-treatment. Tetrandrine caused AVO and MDC induction in SAS cells in a concentration-dependent manner by fluorescence microscopy. Tetrandrine also caused LC-3 expression in SAS cells in a time-dependent manner. Our results show that tetrandrine treatment induced the levels of cleaved caspase-3 in a concentration-and time-dependent manner. Tetrandrine treatment induced the levels of LC-3 II, Atg-5, beclin-1, p-S6, p-ULK, p-mTOR, p-Akt (S473) and raptor. Tetrandrine decreased cell viability, but bafilomycin A1, 3-MA, chloroquine and NAC protected tetrandrine-treated SAS cells against decrease of cell viability. Atg-5, beclin-1 siRNA decreased tetrandrineinduced cleaved caspase-3 and cleaved PARP in SAS cells and protected tetrandrine-treated SAS cells against decrease in cell viability. Chloroquine, NAC and bafilomycin A1 also decreased tetrandrine-induced cleaved caspase-3 and cleaved PARP in SAS cells. Our results indicate the tetrandrine induces apoptosis and autophagy of SAS human cancer cells via caspase-dependent and LC3-I and LC3-II-dependent pathways.

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Section: Methodsmentioning

confidence: 99%

“…Oral cancer is one of the common cancers and is the fourth leading cause of cancer death in Taiwan male population but the 16th in females (1)(2)(3). Based on the 2008 report from the Department of Health, R.O.C.…”

Section: Introductionmentioning

confidence: 99%

Tetrandrine induces cell death in SAS human oral cancer cells through caspase activation-dependent apoptosis and LC3-I and LC3-II activation-dependent autophagy

Huang¹,

Lien

Meng

et al. 2013

International Journal of Oncology

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“…mutation might be in linkage disequilibrium (LD) with other mutations or SNPs involved in the regulation of gene expression. The existence of LD between the c.-1310C¨G and other mutations in Ku70 has also been hypothesized by Tsai et al (22) and Bau et al (29).…”

Section: ------------------------------------------------------------mentioning

confidence: 54%

Discrepancies between in silico and in vitro data in the functional analysis of a breast cancer-associated polymorphism in the XRCC6/Ku70 gene

Marras

Willems²,

Vandersickel³

et al. 2008

Mol Med Rep

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Abstract.Previous results from our research group have shown that the c.-1310 C¨G single nucleotide polymorphism in the promoter region of the XRCC6/Ku70 gene is significantly associated with breast cancer in a sample human patient population. In an attempt to attribute a functional meaning to this polymorphism, we performed a thorough analysis using a number of established in silico tools that strongly suggested that the c.-1310C¨G transversion would activate a cryptic splicing acceptor located upstream of the canonical promoter of Ku70, but downstream of a putative alternative promoter (PAP) of the same gene. Experimental investigation of alternative transcripts, as well as of the activity of the PAP detected in silico, did not support the initial hypothesis of a functional role of the c.-1310C¨G mutation in alternative splicing. Although a functional role of the SNP has yet to be determined, some evidence points to the linkage disequilibrium of the G variant of the polymorphism, with mutations located at critical sites within the promoter region of Ku70. IntroductionBreast cancer is a major public health issue worldwide. Globally, it is by far the most frequent cancer in women, with an estimated 1.15 million new cases in 2002 (23% of all cancers), and more than half of these cases occurring in the industrialized countries of Europe and North America (1). In Europe in 2006, breast cancer accounted for 28.9% of all cancer cases in women, and was the leading cause of cancerrelated death within the European Union (16.7%) (2).In several independent studies also conducted by our group, an enhanced in vitro chromosomal radiosensitivity was observed in a significant number of breast cancer patients (3-7). Since the most detrimental form of radiation-induced DNA damage is the double-strand break (DSB), it is plausible that DSB-initiated chromosomal instability drives breast carcinogenesis. Furthermore, the key breast cancer susceptibility genes, BRCA1 and BRCA2, ATM and TP53, play important roles in DSB repair and chromosome stability (8,9). These genetic factors are present in only 6-11% of the general breast cancer patient population, indicating that other mutations in low penetrant genes or subtle defects arising from low penetrant variations in highly penetrant genes may also create a predisposition to breast cancer (9-12). Recently, several population-based case-control studies have shown a link between single nucleotide polymorphisms (SNPs) in DSB repair genes and breast cancer risk (8,9,(12)(13)(14)(15)(16)(17). Moreover, the breast is a selected microenvironment, subjected to endogenous oxidative stress through hormone exposure. Estrogen in particular has attracted considerable attention, as it may act as a complete carcinogen (8). During the oxidative metabolism of estrogen, reactive oxygen species (ROS) and DNA adducts are formed, leading to the oxidation and depurination of the DNA (18). This type of damage can further result in clustered sites of DNA damage, including DSBs. DSBs are also induced in prolife...

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“…Genetic polymorphisms in DNA repair genes such as EXO1 are thought to modulate DNA repair capacity and consequently are suggested to be associated with colorectal cancer [22]. Singlenucleotide polymorphism (SNP) is a DNA sequence variation and has a great potential application to determine association with susceptibility to several cancers such as oral, breast, prostate, gastric and colorectal cancer [23][24][25][26][27][28][29][30][31]. These indicate that substitution in these SNPs may effect on genes' functions or expression levels.…”

Section: Introductionmentioning

confidence: 99%

“…So, risky genotypes have an effect on cancer susceptibility [20]. Wu et al [32] reported 12 missense single nucleotide polymorphisms in the EXO1 gene including K589E in exon11 [21][22][23][24][25][26][27][28][29][30][31][32]. An exonic SNP doesn't necessarily cause a dysfunctional protein.…”

Section: Introductionmentioning

confidence: 99%

Single Nucleotide Polymorphism (K589E) of the EXO1 Gene: Association with Colorectal Cancer Susceptibility and Clinicopathological Features

Aghdaei¹

2014

GHOA

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Background and aim: Exonuclease1 (EXO1) is a member of the RAD2 nuclease family which is involved in mismatch repair (MMR) system and contributes to the maintenance of genomic stability, modulation of DNA recombination and cell cycle arrest mediation. K589E (rs1047840) as a potentially functional polymorphism in EXO1 gene may alter cancer risk by influencing its repair activity. Method:We designed a case-control study consisting of 319 subjects with colorectal cancer (CRC) and 310 healthy controls to investigate the effect of K589E polymorphism on CRC susceptibility and clinicopathological features in an Iranian population. Genotype determination was performed by PCR-RFLP method. Results:We provided the first evidence that there is not any significant association between EXO1 K589E alleles and genotypes and risk of CRC, even after adjustment for sex, age and smoking status (OR=1.033; 95% CI 0.814-1.312). Also analysis of clinicopathological characteristics and genotype distribution did not show any significant correlation. Conclusion:Despite the well-known role of EXO1, our results revealed that EXO1 K589E polymorphism could not be a potential predisposing risk factor in genetic susceptibility to CRC, at least in the studied population. A large scale case-control study will need to be carried out to further validate this polymorphism as a noncontributor to the risk of CRC in Iranian population.

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Oral cancer and genetic polymorphism of DNA double strand break gene Ku70 in Taiwan

Cited by 58 publications

References 17 publications

Tetrandrine induces cell death in SAS human oral cancer cells through caspase activation-dependent apoptosis and LC3-I and LC3-II activation-dependent autophagy

Tetrandrine induces cell death in SAS human oral cancer cells through caspase activation-dependent apoptosis and LC3-I and LC3-II activation-dependent autophagy

Discrepancies between in silico and in vitro data in the functional analysis of a breast cancer-associated polymorphism in the XRCC6/Ku70 gene

Single Nucleotide Polymorphism (K589E) of the EXO1 Gene: Association with Colorectal Cancer Susceptibility and Clinicopathological Features

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