Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The paxillin gene (PXN) encodes a focal adhesion associated protein that could be involved in the progression of lung cancer through its interactions with the actin cytoskeleton and key signal transduction oncogenes. PXN mutations and PXN amplifications were recently identified in nonsmall-cell lung cancer (NSCLC) and amplifications were associated with MET increased copy number. The description of tumors with two to three mutations in the PXN gene and the overrepresentation of GC to AT transitions were unexpected and needed confirmation. The aim of this study was to validate the incidence of PXN somatic alterations in NSCLC and to correlate them to other common genetic alterations. PXN mutations and copy number changes at PXN, EGFR, and MET loci were analyzed on DNAs from frozen tumor samples (n = 159) that had been previously screened for mutations at EGFR, KRAS, BRAF, ERBB2, STK11, PIK3CA, and TP53. We found PXN polymorphisms including nonsynonymous ones but no PXN amplification and only 1/159 (<1%) somatic tumor mutation F416L. In conclusion, we do not deny the possible involvement of PXN in cancer but our findings do not support a major role for PXN somatic changes in lung carcinogenesis.
 ...
PMID:No somatic genetic change in the paxillin gene in nonsmall-cell lung cancer. 1935 96

Autophagy constitutes one of the major responses to stress in eukaryotic cells, and is regulated by a complex network of signaling cascades. Not surprisingly, autophagy is implicated in multiple pathological processes, including infection by pathogens, inflammatory bowel disease, neurodegeneration and cancer. Both oncogenesis and tumor survival are influenced by perturbations of the molecular machinery that controls autophagy. Numerous oncoproteins, including phosphatidylinositol 3-kinase, Akt1 and anti-apoptotic members of the Bcl-2 family suppress autophagy. Conversely, several tumor suppressor proteins (e.g., Atg4c; beclin 1; Bif-1; BH3-only proteins; death-associated protein kinase 1; LKB1/STK11; PTEN; UVRAG) promote the autophagic pathway. This does not entirely apply to p53, one of the most important tumor suppressor proteins, which regulates autophagy in an ambiguous fashion, depending on its subcellular localization. Irrespective of the controversial role of p53, basal levels of autophagy appear to inhibit tumor development. On the contrary, chemotherapy- and metabolic stress-induced activation of the autophagic pathway reportedly contribute to the survival of formed tumors, thereby favoring resistance. In this context, autophagy inhibition would represent a major therapeutic target for chemosensitization. Here, we will review the current knowledge on the dual role of autophagy as an anti- and pro-tumor mechanism.
 ...
PMID:Anti- and pro-tumor functions of autophagy. 1937 98

Lung cancer is the major cancer killer worldwide, and 5-yr survival is extremely poor (<or=15%), accentuating the need for more effective therapeutic strategies. Significant advances in lung cancer biology may lead to customised therapy based on targeting specific genes and pathways. The main signalling pathways that could provide roadmaps for therapy include the following: growth promoting pathways (Epidermal Growth Factor Receptor/Ras/PhosphatidylInositol 3-Kinase), growth inhibitory pathways (p53/Rb/P14(ARF), STK11), apoptotic pathways (Bcl-2/Bax/Fas/FasL), DNA repair and immortalisation genes. Epigenetic changes in lung cancer contribute strongly to cell transformation by modifying chromatin structures and the specific expression of genes; these include DNA methylation, histone and chromatin protein modification, and micro-RNA, all of which are responsible for the silencing of tumour suppressor genes while enhancing expression of oncogenes. The genetic and epigenetic pathways involved in lung tumorigenesis differ between smokers and nonsmokers, and are tools for cancer diagnosis, prognosis, clinical follow-up and targeted therapies.
 ...
PMID:Pathogenesis of lung cancer signalling pathways: roadmap for therapies. 1948 50

Several female malignancies including breast, ovarian, and endometrial cancers can be characterized based on known somatic and germline mutations. Initiation and propagation of tumors reflect underlying genomic alterations such as mutations, polymorphisms, and copy number variations found in genes of multiple cellular pathways. The contributions of any single genetic variation or mutation in a population depend on its frequency and penetrance as well as tissue-specific functionality. Genome wide association studies, fluorescence in situ hybridization, comparative genomic hybridization, and candidate gene studies have enumerated genetic contributors to cancers in women. These include p53, BRCA1, BRCA2, STK11, PTEN, CHEK2, ATM, BRIP1, PALB2, FGFR2, TGFB1, MDM2, MDM4 as well as several other chromosomal loci. Based on the heterogeneity within a specific tumor type, a combination of genomic alterations defines the cancer subtype, biologic behavior, and in some cases, response to therapeutics. Consideration of tumor heterogeneity is therefore important in the critical analysis of gene associations in cancer.
 ...
PMID:Germline mutations and polymorphisms in the origins of cancers in women. 2011 35

Our understanding of hereditary forms of breast cancer has made enormous advances over the past 15 years, based on epidemiological and molecular genetic studies, and the development of a vast number of informative genetic markers. These studies have involved women with both familial and sporadic forms of breast cancer. Genetic susceptibility to breast cancer can involve several modes of inheritance: Mendelian inheritance, mostly involving autosomal dominant mutations with high penetrance and a high risk of malignancy (the BRCA1, BRCA2, TP53, PTEN and STK11 genes); dominant mutations associated with a lower risk (ATM, BRIP1, PALB2, etc), and multigenic patterns involving common susceptibility variants, i.e., polymorphisms located within predisposing gene loci (FGFR2, TNRC9, MAP3K1, LSP1, etc.) or intergenic regions. Other predisposing factors remain to be discovered, as genetic factors associated with a high breast cancer risk (BRCA1, BRCA2, TP53, PTEN STK11, etc) are only found in about 20% of genetically screened breast cancer families. So far, only the first class of genes have found clinical applications, guiding the choice of medical or surgical treatment. More refined individual risk profiles will benefit from genome-wide polymorphic DNA variant studies anda better understanding of the impact of non genetic factors, such as the obstetrical and gynaecological history, and mutagen exposure.
 ...
PMID:[Implications of genetic risk factors in breast cancer: culprit genes and associated malignancies]. 2069 Feb 7

Pancreatic adenocarcinoma is one of the most aggressive human cancers. It displays many different chromosomal abnormalities and mutations. By using 244 K high-resolution array-comparative genomic hybridization (aCGH) we studied the genome alterations of 39 fine-needle aspirations from pancreatic adenocarcinoma and eight human adenocarcinoma pancreatic cell lines. Using both visual inspection and GISTIC analysis, recurrent losses were observed on 1p, 3p, 4p, 6, 8p, 9, 10, 11q, 15q, 17, 18, 19p, 20p, 21, and 22 and comprised several known or suspected tumor suppressor genes such as ARHGEF10, ARID1A, CDKN2A/B, FHIT, PTEN, RB1, RUNX1-3, SMAD4, STK11/LKB1, TP53, and TUSC3. Heterozygous deletion of the 1p35-p36 chromosomal region was identified in one-third of the tumors and three of the cell lines. This region, commonly deleted in human cancers, contains several tumor suppressor genes including ARID1A and RUNX3. We identified frequent genetic gains on chromosome arms 1q, 3q, 5p, 6p, 7q, 8q, 12q, 15q, 18q, 19q, and 20q. Amplifications were observed in 16 tumors. AKT2, CCND3, CDK4, FOXA2, GATA6, MDM2, MYC, and SMURF1 genes were gained or amplified. The most obvious amplification was located at 18q11.2 and targeted the GATA6 gene, which plays a predominant role in the initial specification of the pancreas and in pancreatic cell type differentiation. In conclusion, we have identified novel biomarkers and potential therapeutic targets in pancreatic adenocarcinoma.
 ...
PMID:Genome profiling of pancreatic adenocarcinoma. 2141 32

The aim of this study was to selectively profile the activation status of mammalian target of rapamycin (mTOR)-associated oncogenes and tumor suppressor genes (TSGs) in ovarian cancer specimens, healthy ovaries and benign ovarian tumors, including endometrial cysts. We used a novel type of microfluidic gene array to examine the expression of 15 human tumor suppressors and oncogenes in ovarian cancer specimens of 53 patients, benign ovarian cysts of 29 women (endometrial and simple) and 11 healthy ovaries of individuals in whom the material was obtained during total hysterectomies performed because of fibroid changes. The array was custom-designed to include the following genes: NF1, RHEB, mTOR1, AKT-1, PTEN, TSC1, TSC2, KRAS, RPS6KB1, 4EBP1, TP53, EIF4E, STK11, PIK3CA and BECN1. Confirmatory immunohistochemical detection was performed for a group of selected proteins. Particularly significant differences were observed as to the expression of PTEN (p < 0.0001), TP53 (p = 0.0003), PIK3CA (p = 0.0003) and BECN1 (p = 0.0014) which were shown to be downregulated in cancer patients when compared to healthy ovaries and benign ovarian cysts (endometrial and simple). These markers did not show association with grade or stage of the tumor. Immunohistochemistry showed that PTEN, TP53, PIK3CA and BECN1 proteins are expressed in ovarian cancer. Our results indicate that there are significant differences in the expression of some of the mTOR-related tumor suppressors and oncogenes which could be associated with the pathogenesis of ovarian cancer.
 ...
PMID:Selective gene expression profiling of mTOR-associated tumor suppressor and oncogenes in ovarian cancer. 2174 34

The incidence of canine mammary tumours (CMTs) differs significantly between breeds, strongly supporting an influence of genetic risk factors. We aimed at identifying germline genetic variations in mammary tumour-associated genes in dogs and survey whether these might alter the encoded proteins. We sequenced 11 genes (BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EGFR, ESR1, HER2, PTEN, STK11 and TP53) and screened for genetic variations. Sixty-four single nucleotide polymorphisms (SNPs) were identified. Nine of the coding SNPs were non-synonymous, of which four were located in gene regions conserved across four species. Three of the non-synonymous SNPs might be damaging according to PolyPhen predictions. One of the indels identified has previously been associated with CMTs. Because of the founder effects, genetic drift and inbreeding in many dog breeds the allele frequencies of the genes studied are likely to vary significantly between breeds and contribute to the considerable difference in genetic risk associated with cancer.
 ...
PMID:Identification of genetic variation in 11 candidate genes of canine mammary tumour. 2207 4

Approximately 5-10% of breast cancers may be inheritable, up to 90% of which are due to mutations in BRCA1 and BRCA2. A substantial minority are caused by non-BRCA mutations, such as TP53, PTEN, STK11, CHEK2, ATM, BRIP1, and PALB2 mutations. This review highlights translational research advances with regard to the development of probabilistic models for hereditary breast cancer syndromes, the identification of specific genetic mutations responsible for these syndromes, as well as their testing and interpretations.
 ...
PMID:Translational advances regarding hereditary breast cancer syndromes. 2244 95

Gastric cancer is a global public health concern, ranking as the fourth leading cause of cancer mortality, with a 5-year survival of only 20%. Approximately 10% of gastric cancers appear to have a familial predisposition, and about half of these can be attributed to hereditary germline mutations. We review the genetic syndromes and current standards for genetic counseling, testing, and medical management for screening and treatment of gastric cancer. Recently, germline mutations in the E-cadherin/CDH1 gene have been identified in families with an autosomal dominant inherited predisposition to gastric cancer of the diffuse type. The cumulative lifetime risk of developing gastric cancer in CDH1 mutation carriers is up to 80%, and women from these families also have an increased risk for developing lobular breast cancer. Prophylactic gastrectomies are recommended in unaffected CDH1 mutation carriers, because screening endoscopic examinations and blind biopsies have proven inadequate for surveillance. In addition to this syndrome, gastric cancer risk is elevated in Lynch syndrome associated with germline mutations in DNA mismatch repair genes and microsatellite instability, in hereditary breast and ovarian cancer syndrome due to germline BRCA1 and BRCA2 mutations, in familial adenomatous polyposis caused by germline APC mutations, in Li-Fraumeni syndrome due to germline p53 mutations, in Peutz-Jeghers syndrome associated with germline STK11 mutations, and in juvenile polyposis syndrome associated with germline mutations in the SMAD4 and BMPR1A genes. Guidelines for genetic testing, counseling, and management of individuals with hereditary diffuse gastric cancer are suggested. A raised awareness among the physician and genetic counseling communities regarding these syndromes may allow for increased detection and prevention of gastric cancers in these high-risk individuals.
 ...
PMID:Genetic testing by cancer site: stomach. 2284 38


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