Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RhoE, a small G protein, is constitutively GTP bound within the cell and can regulate actin cytoskeleton reorganization, leading to the appearance of aggregates of actin filaments. Although emerging evidence suggests that RhoE is causally involved in cancer formation and progression, little is known about its significance in solid cancer, including lung cancer. In the present study, the expression of RhoE was analyzed using Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR), real-time RT-PCR, immunohistochemistry and western blot in 30 patients with Non-small Cell Lung Cancer (NSCLC). Then the correlation of RhoE overexpression with clinical parameters was evaluated. Furthermore, the possible reasons contributing to the RhoE expression were examined by real-time genomic PCR and mutation analysis on DNA sequence and cDNA sequence. Our results revealed that RhoE expression was dramatically increased in lung cancer tissues compared with adjacent nontumoral lung tissues (p <0.01). Immunohistochemistry showed a strong cytoplasmic staining in cancer cells compared with positive membrane staining in adjacent nontumoral proliferative alveolar epitheliums. Moreover, the overexpression of RhoE was significantly associated with the patients' smoking history (p <0.05). 72% tumor tissues displayed DNA copy number changes based on the DNA levels in the matched adjacent nontumoral lung tissues and this copy number changes correlated significantly with RhoE expression and smoking history (p <0.05). Three polymorphisms were identified but no correlation was found with the clinicopathological features. To our knowledge, this is the first report demonstrating that overexpression of RhoE correlated with smoking and DNA copy number changes, suggesting that RhoE may serve as a molecular marker to identify high-risk individuals and assist in the identification of additional pathways of carcinogenesis.
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PMID:Overexpression of RhoE in Non-small Cell Lung Cancer (NSCLC) is associated with smoking and correlates with DNA copy number changes. 1731 84

Human papillomavirus (HPV) is considered to be a necessary but not sufficient cause for cervical cancer. The host immunogenetic background plays an important role in the persistence of HPV infection and subsequent development of cervical cancer. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a molecule expressed mainly on activated T cells and is important in the down-regulation of T-cell activation. The aim of this study was to determine if polymorphisms of the CTLA-4 gene are associated with HPV-induced cervical cancer in Taiwanese women. Polymerase chain reaction-restriction fragment length polymorphism was used to genotype -318 C/T, +49 A/G and CT60 A/G polymorphisms in 144 women with cervical squamous cell carcinoma (CSCC) and 378 ethnicity-matched healthy control women. The presence and genotypes of HPV in CSCC were determined by E6-, E7-based nested polymerase chain reaction. The frequency of C/T genotype of -318 C/T polymorphism was significantly higher in patients with HPV-16-positive CSCC compared with controls (odds ratio = 1.99, 95% confidence interval = 1.16-3.42, P(c) = 0.03). No significant associations were found for +49 A/G and CT60 A/G polymorphisms. Analysis of haplotypes, computationally inferred from genotype data, also revealed no significant differences in distribution among all subjects with CSCC, those with HPV-16-positive CSCC and controls. Our results suggest that the -318 C/T variant in the promoter region of the CTLA-4 gene is associated with HPV-16-associated CSCC in Taiwanese women.
Carcinogenesis 2007 Jun
PMID:CTLA-4 gene and susceptibility to human papillomavirus-16-associated cervical squamous cell carcinoma in Taiwanese women. 1734 58

The aim of this study was to determine p16 gene mutation, deletion, and promoter 5' CpG island hypermethylation in peripheral blood mononuclear leukocyte of patients with arseniasis as attributed to exposure to indoor unventilated coal stove. The role of the aberrant change of p16 gene in the induction and development of carcinogenesis in endemic arsenisiasis region in China was also examined. Polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP), multiplex PCR (mPCR), methylation-specific PCR (MSP), and sequencing techniques were performed to detect (1) mutation of the p16 gene exon 2, (2) homozygous deletion of the p16 gene exon 1 and exon 2, and (3) hypermethylation of the promoter CpG island in peripheral blood mononuclear leukocyte of patients with arseniasis. Results showed no mutation was found in exon 2 of p16 gene. The homozygous deletion frequency of p16 gene was 5 and 15% in control and arseniasis patients, respectively. The homozygous deletion occurred mainly in exon 2, with significant deletion frequencies of 9, 13, and 20% in mild, intermediate, and severe arseniasis groups. The significant homozygous deletion frequency was 9 and 39% in noncarcinoma and carcinoma individuals. The positive rate of p16 gene promoter CpG island hyermethylation was 42 and 2% in the exposed group and the control group, respectively. The positive rate was 26, 42, and 50% in mild, intermediate, and severe arseniasis. The marked different positive rate was 22 and 56% in noncarcinoma and carcinoma individuals, respectively. In conclusion, homozygous deletion and hypermethylation of p16 gene may play an important role in the initiation and development of manifestations seen in endemic arseniasis including carcinogenesis.
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PMID:Analysis of p16 gene mutation, deletion and methylation in patients with arseniasis produced by indoor unventilated-stove coal usage in Guizhou, China. 1747 13

Arsenic is an important environmental carcinogen that affects millions of people worldwide through contaminated water supplies. Chronic exposure of arsenic has been shown to induce malignant transformation of mammalian cells; however, the mechanism underlying arsenic-induced carcinogenesis is not clear. The (1) induction in the cell proliferation, (2) decrease in DNA repair capacity resulting in the accumulation of mutations, and (3) changes in the DNA methylation patterns affecting regulation of genes are hallmarks of cancer development. Thus, the purpose of this study was to determine whether long-term exposure of both low and high concentrations of arsenic can perturb cell proliferation, DNA repair, and the maintenance of DNA methylation status in TM3 cells, an immortalized Leydig cell derived from normal mouse testis. The effect of arsenic on cell proliferation was determined by cell count data, and arsenic-induced gene expression changes were measured by quantitative real-time polymerase chain reduction (PCR). The results this study revealed a concentration-dependent induction of cell proliferation by arsenic. Increased expression of cell proliferation marker genes (PCNA, CyclinD1) and DNA methylation (DNA Methyl Transferase I) and decreased expression of genes for DNA repair (DNA Polymerase beta, ERCC6) with lower concentrations of arsenic was also observed. Thus, the findings of this study are novel, as they indicate a mechanism for arsenic-induced cancers. This is based on the observed increase in cell proliferation and decrease in the capacity of cells to maintain its genomic stability. Our study provides the evidence that arsenic may play a role in the etiology of testicular cancer.
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PMID:Gene expression changes and induction of cell proliferation by chronic exposure to arsenic of mouse testicular Leydig cells. 1755 10

We studied the expression and mutation of thyroid transcription factor-1 (TTF-1) gene in 92 cases of lung carcinomas comprised of lung adenocarcinoma (36 cases), squamous cell lung carcinoma (42 cases), small cell lung carcinoma (8 cases), and large cell lung carcinoma (6 cases) to investigate whether TTF-1 gene mutation predisposed to the development of lung cancer. Normal lung tissues were obtained from each of the 92 patients. The tissues served as controls. Polymerase chain reaction-single-strand conformation polymorphism, denaturing high-performance liquid chromatography, and DNA sequencing were used to analyze TTF-1 gene mutation and its relationship with the carcinogenesis of lung cancer. We detected the expression of TTF-1 protein and messenger RNA (mRNA) in paraffin-embedded lung carcinomas and their normal lung tissues by tissue microarray. TTF-1 protein and mRNA intensities were measured by Leica-Q500 MC Image Analysis System to reveal their correlation with TTF-1 mutation in lung carcinomas. TTF-1 gene missense and synonymous mutation are present in lung carcinomas with the mutation rate of 16%. TTF-1 protein and mRNA are higher in normal lung tissues than in different lung carcinomas. TTF-1 gene mutation is correlated with the loss of TTF-1 protein and mRNA. The analyses of TTF-1 gene missense mutation and synonymous mutation and the loss of TTF-1 protein and mRNA can be regarded as the important indexes of molecular pathology of lung carcinoma.
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PMID:Mutational analysis of thyroid transcription factor-1 gene (TTF-1) in lung carcinomas. 1807 37

This investigation is the first to evaluate simultaneously human papilloma virus (HPV) status, p16(INK4a), and p53 immunoreactivity in epithelial ovarian neoplasms. The results were analyzed and correlated with histological type, histological grade, and survival of patients. Subtypes considered are papillary serous and mucinous. Polymerase chain reaction (PCR) analysis, performed in our previous study, had already demonstrated a small number of HPV-positive epithelial ovarian neoplasms. No significant correlation was found between the presence of HPV DNA and subtypes of ovarian neoplasms; thus, HPV cannot be considered responsible for epithelial ovarian neoplasm. Since p16 immunoreactivity was present in many other HPV-negative cases of epithelial ovarian neoplasms, this study suggests that p16 overexpression in some neoplasms of the female genital tract is not related to HPV carcinogenesis. A higher p53 expression rate observed between borderline and malignant serous tumors and between serous and mucinous neoplasms can confirm a recent dualistic model of ovarian carcinogenesis. According to this theory, low-grade serous carcinomas (serous intraepithelial carcinomas, serous borderline neoplasm, and ovarian mucinous neoplasms) (type I tumors) develop from mutations of KAS and BRAF, while high-grade serous carcinomas (type II tumors) develop from mutation of p53. In malignant neoplasms, for univariate analysis, patient survival seems to be related to p53, strong and diffuse p16 overexpression, and the stage of development of neoplasms at the diagnosis. In multinomial logistic regression, used to evaluate the role of staging, grading, p16 and p53 immunopositivity as predictor variables of unfavorable outcome of the disease, only p16 positivity was significantly related to the poor prognosis of the cancer.
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PMID:Human papilloma virus (HPV) status, p16INK4a, and p53 overexpression in epithelial malignant and borderline ovarian neoplasms. 1818 Jan 13

Parathyroid carcinoma is a rare neoplasm that accounts for only 1-3% of cases of primary hyperparathyroidism. Parathyroid carcinoma is a well-differentiated tumor that is sometimes difficult to differentiate histopathologically from its benign counterpart, parathyroid adenoma. The molecular mechanism of parathyroid carcinogenesis remains unknown, and investigators have reported that abnormalities of the p53 gene do not play a significant role in parathyroid carcinogenesis, unlike in other human malignancies. The present report describes parathyroid carcinoma with anaplastic transformation of differentiated parathyroid carcinoma in a patient with primary hyperparathyroidism. Nuclear accumulation of p53 protein was found in anaplastic carcinoma cells but not in differentiated carcinoma cells. Polymerase chain reaction-single-strand conformation polymorphism followed by direct sequencing showed that anaplastic carcinoma cells carried a missense mutation at codon 248 (CGG to CAG) of the p53 gene, while the remaining differentiated carcinoma cells had the wild-type p53 gene. These findings suggest that the p53 gene mutation is associated with anaplastic transformation of parathyroid carcinoma.
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PMID:Parathyroid carcinoma with anaplastic feature: association of a p53 gene mutation with anaplastic transformation. 1915 65

Nuclear factor-kappaB (NF-kappaB) is a transcription factor responsible for modulating the expression of many genes involved in immune response, inflammatory process, cell growth and survival. A functional and common promoter polymorphism of the NF-kappaB1 (NFKB1) gene leads to alteration in the activation pattern and expression of NF-kappaB, and thus, is probably associated with carcinogenesis. The aim of this study was to detect the importance and the frequency of NFKB1 -94 insertion/deletion ATTG promoter polymorphism in patients with gastroenteropancreatic neuroendocrine tumor. A case-control cohort including 50 patients with gastroenteropancreatic neuroendocrine tumor and 100 healthy controls was genotyped with the polymerase chain reaction method. Polymerase chain reaction products were analyzed in agarose gel electrophoresis and processed with the Van91I restriction enzyme. There are 2 cleavage points on the amplified region. When ATTG insertion or deletion is present, the function of restriction enzyme changes. Thirty patients (60%) had ID (insertion/deletion), 18 (36%) had II (insertion/insertion) and 2 (4%) had DD (deletion/deletion) genotypes. Fifty-eight of the control group (58%) had ID, 30 (30%) had II and 12 (12%) had DD genotypes. The frequencies of D and I alleles were 34 and 66 in the study group, and 82 and 118 in the control group, respectively. Although the frequencies of I and D alleles and genotype distribution did not differ between the study and control groups, there seem to be important differences concerning the DD genotype analyses of the NFKB1 -94ins/delATTG promoter polymorphism between patients with pancreatic neuroendocrine tumor and those with carcinoid tumor. This may support the view that the genetics of carcinoid tumors and pancreatic neuroendocrine tumors are different and should be further studied.
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PMID:NFKB1 -94 insertion/deletion ATTG polymorphism in gastroenteropancreatic neuroendocrine tumors. 1975 53

Among gynecological malignancies, ovarian cancer is the leading cause of death. The overall 5-year survival rate remains poor, and the pathogenesis is unknown. The interleukin-23 receptor (IL23R) is known to be critically involved in the carcinogenesis of different malignant tumors. To assess the role of IL23R in ovarian cancer, we conducted a study to investigate the polymorphisms of the IL23R gene in 96 Han Chinese women with histologically proven ovarian cancer. Polymerase chain reaction-restriction fragment length polymorphism was used for genotyping. In all three single nucleotide polymorphisms of IL23R studied, the distribution of genotype and allele frequencies of rs10889677 differed significantly between patients and controls. The frequency of allele C of rs10889677 was significantly increased in cases compared with controls (0.281 vs. 0.183, odds ratio OR=1.752, 95% confidence interval CI=1.107-2.772). Furthermore, when stratified by tumor stage, we found that the allele frequencies of rs11465817 differed significantly between FIGO stage I+II and III+IV. The higher frequency of allele A was significantly associated with advanced ovarian cancer (P=0.027, OR=2.087, 95% CI=1.083-4.023). These findings indicate that IL23R polymorphisms may play an important role in the susceptibility and prognosis of ovarian cancer in the Chinese population.
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PMID:Association of interleukin-23 receptor gene polymorphisms with risk of ovarian cancer. 2008 50

During the development of tissues, complex programs take place to reach terminally differentiated states with specific gene expression profiles. Epigenetic regulations such as histone modifications and chromatin condensation have been implicated in the short and long-term control of transcription. It has recently been shown that the 3D spatial organization of chromosomes in the nucleus also plays a role in genome function. Indeed, the eukaryotic interphase nucleus contains sub-domains that are characterized by their enrichment in specific factors such as RNA Polymerase II, splicing machineries or heterochromatin proteins which render portions of the genome differentially permissive to gene expression. The positioning of individual genes relative to these sub-domains is thought to participate in the control of gene expression as an epigenetic mechanism acting in the nuclear space. Here, we review what is known about the sub-nuclear organization of mammary epithelial cells in connection with gene expression and epigenetics. Throughout differentiation, global changes in nuclear architecture occur, notably with respect to heterochromatin distribution. The positions of mammary-specific genes relative to nuclear sub-compartments varies in response to hormonal stimulation. The contribution of tissue architecture to cell differentiation in the mammary gland is also seen at the level of nuclear organization, which is sensitive to microenvironmental stimuli such as extracellular matrix signaling. In addition, alterations in nuclear organization are concomitant with immortalization and carcinogenesis. Thus, the fate of cells appears to be controlled by complex pathways connecting external signal integration, gene expression, epigenetic modifications and chromatin organization in the nucleus.
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PMID:Epigenetic modifications in 3D: nuclear organization of the differentiating mammary epithelial cell. 2014 38


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