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

We previously performed SEREX (serological identification of antigens by recombinant expression cloning) using the sera of patients with esophageal squamous cell carcinoma (SCC), and isolated a variant clone (AK093616) of ubiquitin-conjugating enzyme E21 (UBE2I). This clone was tentatively designated as UBE2I-v5 and analyzed for biological function by transient transfection of the cDNA into activated Ha-ras-transformed NIH3T3 (ras-NIH) mouse fibroblasts. Chemosensitivity to 92 cytotoxic drugs was compared between UBE2I-v5-transfected cells and the parental ras-NIH cells. The UBE2I-v5-transfected cells were more sensitive than the parental cells to anticancer drugs such as vincristine (VCR), mitoxantrone (MIT) and etoposide (VP16). The regression analysis of the total chemosensitivity pattern of UBE2I-vS-transfected cells revealed that the function of UBE2I-v5 was positively related to RPA2 (replication protein A2), Rho-GDI (Rho guanine nucleotide dissociation inhibitor a), FUS (putative tumor suppressor) and TKT (transketolase) but negatively related to Per-1 (period-I), Ran (nuclear Ras-related protein), PTEN (phosphatase and tensin homolog), C/EBPalpha (CCAAT/enhancer binding protein a) and the tumor suppressor p53. Thus, it is possible that UBE21-v5 plays a role in carcinogenesis by suppressing the function of CIEBPa and/or p53 via RPA2-like activity.
 ...
PMID:Sensitization against anticancer drugs by transfection with UBE2I variant gene into ras-NIH3H3 mouse fibroblasts. 1797 65

GATA-binding protein 3 (GATA3) is a transcription factor and a putative tumor suppressor that is highly expressed in normal breast luminal epithelium and estrogen receptor alpha (ER)-positive breast tumors. We hypothesized that common genetic variation in GATA3 could influence breast carcinogenesis. Four tag single-nucleotide polymorphisms (SNP) in GATA3 and its 3' flanking gene FLJ4598 were genotyped in two case control studies in Norway and Poland (2,726 cases and 3,420 controls). Analyses of pooled data suggested a reduced risk of breast cancer associated with two intronic variants in GATA3 in linkage disequilibrium (rs3802604 in intron 3 and rs570613 in intron 4). Odds ratio (95% confidence interval) for rs570613 heterozygous and rare homozygous versus common homozygous were 0.85 (0.75-1.95) and 0.82 (0.62-0.96), respectively (P(trend)=0.004). Stronger associations were observed for subjects with ER-negative, than ER-positive, tumors (P(heterogeneity)=0.01 for rs3802604; P(heterogeneity)=0.09 for rs570613). Although no individual SNPs were associated with ER-positive tumors, two haplotypes (GGTC in 2% of controls and AATT in 7% of controls) showed significant and consistent associations with increased risk for these tumors when compared with the common haplotype (GATT in 46% of controls): 1.71 (1.27-2.32) and 1.26 (1.03-1.54), respectively. In summary, data from two independent study populations showed two intronic variants in GATA3 associated with overall decreases in breast cancer risk and suggested heterogeneity of these associations by ER status. These differential associations are consistent with markedly different levels of GATA3 protein by ER status. Additional epidemiologic studies are needed to clarify these intriguing relationships.
 ...
PMID:Common genetic variation in GATA-binding protein 3 and differential susceptibility to breast cancer by estrogen receptor alpha tumor status. 1800 15

With the idea to discover novel genes involved in proliferation, we have performed a genome-wide loss-of-function genetic screen to identify additional putative tumor suppressor genes. We have previously identified five genes belonging to different biochemical families. In this report, we focused on the study of one of these genes designated S-adenosylhomocysteine hydrolase (SAHH), which has also been previously identified in an independent short hairpin RNA screening. SAHH inactivation confers resistance to both p53 and p16(INK4)-induced proliferation arrest. Interestingly, SAHH inactivation inhibits p53 transcriptional activity and impairs DNA damage-induced transcription of p21(Cip1). Given that SAHH downregulation modulates senescence in primary cells, we also studied SAHH expression in human tumors at the messenger RNA (mRNA) and protein levels. SAHH mRNA was lost in 50% of tumor tissues from 206 patients with different kinds of tumors in comparison with normal tissue counterparts. Moreover, SAHH protein was also affected in some colon cancers. Such findings may be of relevance to cancer research, suggesting that SAHH might be a largely unexplored tumor suppressor.
Carcinogenesis 2008 Nov
PMID:S-adenosylhomocysteine hydrolase downregulation contributes to tumorigenesis. 1871 39

Colorectal cancers with mutations in the p53 gene have an invasive property, but its underlying mechanism is not fully understood. Through the screening of two data sets of the genome-wide expression profile, one for p53-introduced cells and the other for the numbers of cancer tissues, we report here X-linked ectodermal dysplasia receptor (XEDAR), a member of the TNFR superfamily, as a novel p53 target that has a crucial role in colorectal carcinogenesis. p53 upregulated XEDAR expression through two p53-binding sites within intron 1 of the XEDAR gene. We also found a significant correlation between decreased XEDAR expressions and p53 gene mutations in breast and lung cancer cell lines (P=0.0043 and P=0.0122, respectively). Furthermore, promoter hypermethylation of the XEDAR gene was detected in 20 of 20 colorectal cancer cell lines (100%) and in 6 of 12 colorectal cancer tissues (50%), respectively. Thus, the XEDAR expression was suppressed to <25% of surrounding normal tissues in 12 of 18 colorectal cancer tissues (66.7%) due to either its epigenetic alterations and/or p53 mutations. We also found that XEDAR interacted with and subsequently caused the accumulation of FAS protein, another member of p53-inducible TNFR. Moreover, XEDAR negatively regulated FAK, a central component of focal adhesion. As a result, inactivation of XEDAR resulted in the enhancement of cell adhesion and spreading, as well as resistance to p53-induced apoptosis. Taken together, our findings showed that XEDAR is a putative tumor suppressor that could prevent malignant transformation and tumor progression by regulating apoptosis and anoikis.
 ...
PMID:XEDAR as a putative colorectal tumor suppressor that mediates p53-regulated anoikis pathway. 1954 21

Human papillomavirus (HPV)-induced carcinogenesis is critically dependent on the activities of the viral E6 and E7 oncogenes. Here, we demonstrate that expression of the putative tumor suppressor gene B-cell translocation gene-2 (BTG2) is reinduced in HPV16- and HPV18-positive cancer cells on silencing of viral oncogene expression, indicating that BTG2 is repressed by oncogenic HPVs. Inhibition of BTG2 expression was mediated by the HPV E6 oncogene and occurred in a p53-dependent manner. Luciferase reporter gene analyses revealed that BTG2 repression takes place at the transcriptional level and is dependent on the integrity of the major p53-response element within the BTG2 promoter. Ectopic expression of BTG2 acted antiproliferative in cervical cancer cells. Tissue specimens commonly exhibited reduced BTG2 protein levels in HPV-positive high-grade lesions (CIN2/3) and cervical carcinomas, when compared with normal cervical epithelium. These findings identify the antiproliferative BTG2 gene as a novel cellular target blocked by the HPV E6 oncoprotein.
 ...
PMID:Oncogenic human papillomaviruses block expression of the B-cell translocation gene-2 tumor suppressor gene. 1955 55

A major goal of molecular biology is to elucidate the mechanisms underlying cancer development and progression in order to achieve early detection, better diagnosis and staging and novel preventive and therapeutic strategies. We feel that an understanding of Runt-related transcription factor 3 (RUNX3)-regulated biological pathways will directly impact our knowledge of these areas of human carcinogenesis. The RUNX3 transcription factor is a downstream effector of the transforming growth factor-beta (TGF-beta) signaling pathway, and has a critical role in the regulation of cell proliferation and cell death by apoptosis, and in angiogenesis, cell adhesion and invasion. We previously identified RUNX3 as a major gastric tumor suppressor by establishing a causal relationship between loss of function and gastric carcinogenesis. More recently, we showed that RUNX3 functions as a bona fide initiator of colonic carcinogenesis by linking the Wnt oncogenic and TGF-beta tumor suppressive pathways. Apart from gastric and colorectal cancers, a multitude of epithelial cancers exhibit inactivation of RUNX3, thereby making it a putative tumor suppressor in human neoplasia. This review highlights our current understanding of the molecular mechanisms of RUNX3 inactivation in the context of cancer development and progression.
 ...
PMID:Molecular pathology of RUNX3 in human carcinogenesis. 1968 50

Aberrant promoter methylation of several known or putative tumor suppressor genes occurs frequently during carcinogenesis, and this epigenetic change has been considered as a potential molecular marker for cancer. We examined the methylation status of nine genes (APC, CDH1, CTNNB1, TIMP3, ESR1, GSTP1, MGMT, THBS1, and TMS1), by quantitative methylation specific PCR. Synchronous preinvasive lesions (atypical ductal hyperplasia and/or ductal carcinoma in situ) and invasive ductal breast carcinoma from 52 patients, together with pure lesions from 24 patients and 12 normal tissues paired to tumor and 20 normal breast distant from tumor were analyzed. Aberrant promoter methylation was detected in both preinvasive and invasive lesions for genes APC, CDH1, CTNNB1, TIMP3, ESR1, and GSTP1. However, hierarchical mixed model and Generalized Estimating Equations model analyses showed that only APC, CDH1, and CTNNB1 promoter regions showed a higher frequency and methylation levels in pathologic samples when compared with normal breast. Whereas APC and CTNNB1 did not show differences in methylation levels or frequencies, CDH1 showed higher methylation levels in invasive tumors as compared with preinvasive lesions (P < 0.04, Mann-Whitney test with permutation correction). The analysis of APC, CDH1, and CTNNB1 methylation status was able to distinguish between normal and pathologic samples with a sensitivity of 67% (95% confidence interval, 60-71%) and a specificity of 75% (95% confidence interval, 69-81%). Our data point to the direct involvement of APC, CDH1, and CTNNB1 promoter methylation in the early stages of breast cancer progression and suggest that they may represent a useful tool for the detection of tumor cells in clinical specimens.
 ...
PMID:Changes in CpG islands promoter methylation patterns during ductal breast carcinoma progression. 1978 64

Radiation is a carcinogen, interacting with DNA to produce a range of mutations. Irradiated cells also show genomic instability, as do adjacent non-irradiated cells (the bystander effect); the importance to carcinogenesis remains to be established. Current knowledge of radiation effects is largely dependent on evidence from exposure to atomic bomb whole body radiation, leading to increases in a wide range of malignancies. In contrast, millions of people were exposed to radioactive isotopes in the fallout from the Chernobyl accident, within the first 20 years there was a large increase in thyroid carcinoma incidence and a possible radiation-related increase in breast cancer, but as yet there is no general increase in malignancies. The increase in thyroid carcinoma, attributable to the very large amounts of iodine 131 released, was first noticed in children with a strong relationship between young age at exposure and risk of developing papillary thyroid carcinoma (PTC). The extent of the increase, the reasons for the relationship to age at exposure, the reduction in attributable fraction with increasing latency and the role of environmental factors are discussed. The large number of radiation-induced PTCs has allowed new observations. The subtype and molecular findings change with latency; most early cases were solid PTCs with RET-PTC3 rearrangements, later cases were classical PTCs with RET-PTC1 rearrangements. Small numbers of many other RET rearrangements have occurred in 'Chernobyl' PTCs, and also rearrangement of BRAF. Five of the N-terminal genes found in papillary carcinoma rearrangements are also involved in rearrangements in hematological malignancies; three are putative tumor suppressor genes, and two are further genes fused to RET in PTCs. Radiation causes double-strand breaks; the rearrangements common in these radiation-induced tumors reflect their etiology. It is suggested that oncogenic rearrangements may commonly involve both a tumor-suppressor gene (or a DNA repair gene) as well as an oncogene. Involvement of two relevant genes would give a greater chance of progression and a shorter latency than a single-gene mutation. More information is needed on germline mutations conferring susceptibility to radiation-induced PTCs, particularly DNA repair genes. The radiation exposure to the fallout after Chernobyl was very different from the whole body radiation after the atomic bombs. The type and molecular pathology of the thyroid tumors is changing with increasing latency, long latency tumors in other organs could occur in the future. A comprehensive follow up must continue for the lifetime of those exposed.
 ...
PMID:Radiation carcinogenesis: lessons from Chernobyl. 1995 82

Cell adhesion molecule 1 (CADM1/TSLC1), a putative tumor suppressor involving in cell adhesion, proliferation and apoptosis, is frequently inactivated in several carcinomas due to promoter hypermethylation. But alterations of CADM1/TSLC1 in colorectal carcinogenesis and clinical significance have not been elucidated yet. The aim of this study was to determine the role of functional inactivation of CADM1/TSLC1 gene in colorectal tumorigenesis and its potential as a novel epigenetic marker for clinical assessment of patients with colorectal cancer. We measured CADM1/TSLC1 expression levels in 8 colorectal cancer cell lines, 54 primary colorectal carcinomas and their corresponding non-cancerous tissues by reverse transcription polymerase chain reaction, western blot analysis and immunohistochemistry. We analyzed CADM1/TSLC1 promoter methylation status by bisulfite genomic sequencing and the methylation special polymerase chain reaction, and evaluated its correlation with clinicopathological characteristics. All statistical tests were 2-sides. Downregulation of CADM1/TSLC1 expression was observed in 7 of 8 (88%) colorectal cancer cell lines and in 39 of 54 (72%) primary colorectal carcinomas. Hypermethylation of CADM1/TSLC1 promoter region occurred in 6 of 8 (75%) colorectal cancer cell lines and 32 of 54 (59%) primary colorectal carcinomas, and was correlated with advanced colorectal carcinoma. Epigenetic inactivation of CADM1/TSLC1 gene is a frequent alteration in development of colorectal cancer and can be a potential biomarker for molecular staging of patients with colorectal cancer.
 ...
PMID:CADM1/TSLC1 inactivation by promoter hypermethylation is a frequent event in colorectal carcinogenesis and correlates with late stages of the disease. 2034 Jan 31

MicroRNAs, which are endogenously expressed regulatory noncoding RNAs, have an altered expression in colorectal cancer. The aim of our study was to assess the relationship of miR-21 and miR-143 expression to the prognostic/clinicopathological features of colorectal carcinoma (CRC) and colorectal liver metastases (CLM). The estimation was performed in 46 paired (tumor and control) tissue samples of CRC. Further, we studied 30 tissue samples of CLM. MiR-21 and miR-143 expressions were quantified by using the quantitative reverse transcription polymerase chain reaction method. Relation of miR-21 and miR-143 expression to disease-free interval (DFI) (Wilcoxon; P = 0.0026 and P = 0.0191, respectively) was recorded. There was shorter DFI in patients with a higher expression of miR-21 and, surprisingly, also in patients with a higher expression of miR-143, which is a putative tumor suppressor. There was a higher expression of miR-21 and lower expression of miR-143 in CRC tissue in comparison with adjacent normal colon tissue (P < 0.0001; P < 0.0001, respectively). Similarly, we observed a higher expression of miR-21 and a lower expression of miR-143 in CLM in comparison with normal colon tissue (P < 0.0001; P < 0.0001, respectively). Our results support the hypothesis about oncogenic function of miR-21 and show its relation to DFI. The role of miR-143 in carcinogenesis seems to be more complex.
 ...
PMID:Relevance of miR-21 and miR-143 expression in tissue samples of colorectal carcinoma and its liver metastases. 2062 May 99


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>