Search results for: TP53

Authors: A. Doosti, P. Ghasemi Dehkordi, M. Zamani, S. Taheri, M. Banitalebi, M. Mahmoudzadeh

Abstract:

The p53 tumor suppressor gene plays two important roles in genomic stability: blocking cell proliferation after DNA damage until it has been repaired, and starting apoptosis if the damage is too critical. Codon 72 exon4 polymorphism (Arg72Pro) of the P53 gene has been implicated in cancer risk. Various studies have been done to investigate the status of p53 at codon 72 for arginine (Arg) and proline (Pro) alleles in different populations and also the association of this codon 72 polymorphism with various tumors. Our objective was to investigate the possible association between P53 Arg72Pro polymorphism and susceptibility to colorectal cancer among Isfahan and Chaharmahal Va Bakhtiari (a part of south west of Iran) population. We investigated the status of p53 at codon 72 for Arg/Arg, Arg/Pro and Pro/Pro allele polymorphisms in blood samples from 145 colorectal cancer patients and 140 controls by Nested-PCR of p53 exon 4 and digestion with BstUI restriction enzyme and the DNA fragments were then resolved by electrophoresis in 2% agarose gel. The Pro allele was 279 bp, while the Arg allele was restricted into two fragments of 160 and 119 bp. Among the 145 colorectal cancer cases 49 cases (33.79%) were homozygous for the Arg72 allele (Arg/Arg), 18 cases (12.41%) were homozygous for the Pro72 allele (Pro/Pro) and 78 cases (53.8%) found in heterozygous (Arg/Pro). In conclusion, it can be said that p53Arg/Arg genotype may be correlated with possible increased risk of this kind of cancers in south west of Iran.

Keywords: TP53, Polymorphism, Colorectal Cancer, Iran

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Authors: M. Marjaneh, M. Y. Narazah, H. Shahrul

Abstract:

Array-based gene expression analysis is a powerful tool to profile expression of genes and to generate information on therapeutic effects of new anti-cancer compounds. Anti-apoptotic effect of thymoquinone was studied in MCF7 breast cancer cell line using gene expression profiling with cDNA microarray. The purity and yield of RNA samples were determined using RNeasyPlus Mini kit. The Agilent RNA 6000 NanoLabChip kit evaluated the quantity of the RNA samples. AffinityScript RT oligo-dT promoter primer was used to generate cDNA strands. T7 RNA polymerase was used to convert cDNA to cRNA. The cRNA samples and human universal reference RNA were labelled with Cy-3-CTP and Cy-5-CTP, respectively. Feature Extraction and GeneSpring softwares analysed the data. The single experiment analysis revealed involvement of 64 pathways with up-regulated genes and 78 pathways with downregulated genes. The MAPK and p38-MAPK pathways were inhibited due to the up-regulation of PTPRR gene. The inhibition of p38-MAPK suggested up-regulation of TGF-ß pathway. Inhibition of p38-MAPK caused up-regulation of TP53 and down-regulation of Bcl2 genes indicating involvement of intrinsic apoptotic pathway. Down-regulation of CARD16 gene as an adaptor molecule regulated CASP1 and suggested necrosis-like programmed cell death and involvement of caspase in apoptosis. Furthermore, down-regulation of GPCR, EGF-EGFR signalling pathways suggested reduction of ER. Involvement of AhR pathway which control cytochrome P450 and glucuronidation pathways showed metabolism of Thymoquinone. The findings showed differential expression of several genes in apoptosis pathways with thymoquinone treatment in estrogen receptor-positive breast cancer cells.

Keywords: CARD16, CASP10, cDNA microarray, PTPRR, Thymoquinone.

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