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

Genetic alterations of several oncogenes and tumor suppressor genes are associated with human colorectal carcinogenesis. Especially in mutations, the K-ras, p53, APC and DCC gene frequently occurred, and these gene alterations seem to have important roles in colorectal carcinogenesis. We investigated 28 human colon cancer specimens obtained from surgery and five human colon cancer cell lines by PCR-SSCP assay, PCR-OSH assay, RT-PCR or sequencing method. Forty percent of cancers from surgical specimens had Ki-ras 2 (codon 12/13), p53 (Exon 5-8), APC (MCR) gene mutations, and fifty-seven percent of them had lower expression of DCC gene that of normal matched colon mucosa of the same patient. G to A transition was the most frequent in K-ras mutational spectrum in this case; 25% of patients had both k-ras and p53 gene point mutations. Form the results, we concluded that it in colorectal carcinogenesis for both K-ras and p53 gene point mutations might not necessary occur.
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PMID:[Genetic alterations of human colorectal cancer]. 810 90

Mucin-producing tumors of the pancreas (MPT) are characterized by the production of much mucin and a benign course after surgical treatment. We examined 16 cases of MPT and 20 cases of "common" pancreatic duct cell carcinomas (DCC) in regard to K-ras and p53 mutations. The mutations were detected by constant denaturant gel electrophoresis in combination with other techniques using PCR products amplified from the samples microdissected from the tissue sections. K-ras codon 12 mutations were identified in all MPT and in 95% of DCC. On the other hand, p53 mutations were found in four of 20 (20%) DCC, and p53 was immunocytochemically overexpressed in 3 of the 4 mutated cases. However, no p53 mutations and no p53 overexpression were identified in the 16 MPT. These results indicate that, although the K-ras codon 12 mutations may be almost essential for the development of both MPT and DCC, p53 mutations seemed to be involved mainly to the latters.
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PMID:Frequent K-ras mutations and absence of p53 mutations in mucin-producing tumors of the pancreas. 812 Nov 90

We describe the spontaneous progression of a colon adenoma cell line to tumorigenicity and growth factor independence. This system allows direct comparison of biologic stages of malignant progression with alterations of colon cancer suppressor genes and oncogenes. VACO-235, a human colon adenoma cell line, is at early passages nontumorigenic in the nude mouse, unable to grow in soft agar, growth stimulated by serum and EGF, and growth inhibited by TGF-beta. VACO-235 daughter passages 93 and higher have in culture spontaneously progressed to being weakly tumorigenic, but retain all other growth characteristics of VACO-235 early passages. A mouse xenograft from late passage VACO-235 was reestablished in culture as the granddaughter cell line, VACO-411. VACO-411 is highly tumorigenic, clones in soft agar, and is unresponsive to serum, EGF, and TGF-beta. Early passage VACO-235 bears a mutant K-ras allele, bears only mutant APC alleles, expresses no DCC transcripts, and expresses only wild type p53 transcripts. VACO-411 retains the identical genotype, still expressing only wild type p53. Colonic cells after ras mutation, APC mutation, and DCC inactivation remain nontumorigenic and growth factor dependent. Malignant progression involves at least two additional steps, and in VACO-411 can proceed by a novel pathway not requiring p53 inactivation.
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PMID:A benign cultured colon adenoma bears three genetically altered colon cancer oncogenes, but progresses to tumorigenicity and transforming growth factor-beta independence without inactivating the p53 tumor suppressor gene. 813 40

We studied K-ras and p53 gene mutations in a panel of 57 primary pancreatic cancers including ductal and nonductal tumors. DNAs were obtained from formalin-fixed, paraffin-embedded material. Target sequences were amplified by polymerase chain reaction and analyzed by denaturing gradient gel electrophoresis and sequencing. Both K-ras and p53 genes were frequently mutated in ductal cancers (25 of 35, 71.4%; 18 of 35, 51.4%, respectively). K-ras mutations were confined to the second position of codon 12 where base transitions and transversions were equally observed. p53 changes were mainly missense mutations. Transitions and transversions were found equally with a prevalence of G:C-->A:T changes among transitions. No gene alterations were present in the 6 exocrine nonductal tumors and (with one exception) in the 12 endocrine tumors analyzed. Our results indicate that mutated K-ras and p53 genes can cooperate in the establishment of ductal pancreatic cancers, whereas other genetic events have to be present in nonductal tumors. Moreover, K-ras alterations may represent an early event in ductal tumorigenesis, as suggested both by the high gene mutation frequency and by the presence of mutations in low-grade tumors. On the contrary, p53 gene changes seem to represent an event required for the malignancy progression of ductal tumors from lower to higher grades.
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PMID:K-ras and p53 gene mutations in pancreatic cancer: ductal and nonductal tumors progress through different genetic lesions. 813 63

Mutation of the p53 gene is thought to be a late event in human colorectal carcinogenesis, involved in the malignant conversion of the adenoma to the carcinoma. One of the questions that we hoped to address was whether, in vivo, a single mutational event in one p53 gene is sufficient to confer a significant growth advantage on a colonic epithelial cell. Such a growth advantage could result either from an increase in growth rate and/or loss of response to inhibitory growth signals naturally present in the colonic crypt. We therefore introduced the pC53-SCX3 143 (Val-Ala) p53 mutation into a non tumorigenic adenoma derived cell line, AA/C1, which contained a truncating APC mutation, activating K-ras mutation but was wild-type for the p53 protein. High levels of mutant p53 protein were detected in the pC53-SCX3 transfected AA/C1 cell lines but was found not to affect either the in vitro (colony forming efficiency, anchorage independence) or in vivo (tumorigenicity in nude mice) growth, when compared to vector control or the parental AA/C1 cell line. In addition, to test whether the cells become less sensitive to inhibitory growth factors, the response of the cell lines to the naturally occurring growth inhibitor TGF beta was also investigated. Even though TGF beta had previously been implicated in the control of growth of intestinal epithelium, expression of the mutant p53 protein did not affect the sensitivity of the parental AA/C1 cell line to TGF beta. Under the experimental conditions tested expression of the 143 (Val-Ala) p53 protein was unable to affect the in vitro or in vivo growth characteristics of the adenoma derived AA/C1 cell line. When compared to other studies, these results suggest that the genetic background of the individual recipient cell may greatly influence the effect of expression of a particular p53 mutation.
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PMID:Transfection and expression of mutant p53 protein does not alter the in vivo or in vitro growth characteristics of the AA/C1 human adenoma derived cell line, including sensitivity to transforming growth factor-beta 1. 815 11

Molecular mechanisms of pituitary tumorigenesis were studied using Polymerase chain reaction-single stranded conformational polymorphism with DNA sequencing to identify potential mutations in the ras protooncogenes and the tumor suppressor gene p53 in invasive pituitary adenomas and carcinomas. Sequencing of exons 5 through 8 of the p53 gene revealed no mutations, nor were mutations detected in the N- or K-ras protooncogenes in four of the carcinomas and their respective metastatic deposits. Point mutations of H-ras however, were identified in three distant metastatic pituitary tumor secondaries, but not in their respective primary pituitary carcinomas, or in six invasive adenomas. Two of the mutations included a G to C substitution at codon 12, and a G to A substitution at codon 18, resulting in a glycine to arginine, and an alanine to threonine change at these amino acids, respectively. A third mutation involved a single base pair (adenine) deletion in codon 3 of H-ras which causes a frame shift, resulting in a termination signal at codon 19. These results suggest that point mutations in p53 and ras are not associated with pituitary tumorigenesis, however, point mutations of the H-ras gene may be important in the formation and or growth of pituitary metastases. This observed genomic instability will be of value in predicting the potential metastatic behavior of these aggressive pituitary tumors.
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PMID:H-ras mutations in human pituitary carcinoma metastases. 815 9

We have analyzed K-ras mutations and p53 alterations in 39 tumor and nontumor samples taken from nine patients with longstanding ulcerative colitis and colorectal carcinoma. Two of nine invasive carcinomas contained a K-ras mutation. By a combination of immunohistochemistry and single-strand conformation polymorphism analysis, p53 alterations were found in three of nine carcinomas. Five of 13 dysplastic lesions harbored a mutated K-ras gene, even in the absence of detectable changes in associated invasive tumors. One single focus of dysplastic mucosa harbored concomitant K-ras and p53 gene alterations. In two patients, a K-ras mutation was detected in epithelial lesions considered to be devoid of malignant potential (villous regeneration, active colitis). Our results indicate that: 1) the prevalence of K-ras and p53 genetic alterations found in ulcerative colitis-associated colonic carcinomas appears to be lower than in sporadic carcinomas; 2) K-ras mutations can be detected in dysplasia, villous regeneration, and active colitis and affect a subpopulation of the cells composing the lesions; 3) diverse genetic alterations can be detected in the same patient and the dysplastic lesions can exhibit a different genotype than the carcinomas; and 4) at least part of active colitis and villous regeneration lesions should be considered as preneoplastic in ulcerative colitis.
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PMID:K-ras mutations and p53 alterations in neoplastic and nonneoplastic lesions associated with longstanding ulcerative colitis. 816 Jul 76

Lung cancer arises after a series of morphological changes, which take several years to progress from normal epithelium to invasive cancer. The morphological changes progress from hyperplasia, to metaplasia, to dysplasia, to carcinoma in situ, to invasive cancer and finally to metastatic cancer. Multiple molecular changes have been documented in lung cancers, both small cell (SCLC) and non-small cell (NSCLC) types. The number of changes has been estimated to be in double digits. How can so many changes develop in one cell? One possible explanation is the "field cancerization" theory, that states that all or much of the aerodigestive tract epithelium has been mutagenized, perhaps as the result of exposure to tobacco products or other carcinogens. The molecular changes include activation of dominant oncogenes (myc family, K-ras and HER/2/neu genes), as well as loss of recessive growth regulatory genes or anti-oncogenes (p53, and rb as well as unidentified gene or genes on chromosome 3). However, cytogenetic and molecular genetic studies indicate that multiple other specific sites of actual or potential DNA loss may be present in lung cancers. Many of the well characterized molecular changes may function as negative prognostic factors for survival in subsets of lung cancers. Other changes may include development of drug resistance, and production of growth factors and their receptors. It is tempting to associate specific molecular changes with specific morphological changes, as has been attempted in the colon. However, because of the difficulties in serially sampling the respiratory tract, only a modest amount of data has been collected to date. It appears that deletions of chromosome 3p, hyperproliferation and aneuploidy are early changes, while p53 mutations appear later in the preneoplastic cascade. Documentation of intermediate markers for lung cancer and prospective studies of their prognostic effects will be necessary for the design of rational chemoprevention trials.
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PMID:The molecular and cellular basis of human lung cancer. 816 65

Mutations in the K-ras oncogene and in the p53 tumor suppressor gene are commonly identified in sporadic cases of pancreatic adenocarcinoma. Although these genes might serve as useful markers for early diagnosis of pancreatic carcinoma in patients at risk for the development of this disease, familial pancreatic carcinomas have not been studied for these mutations. We recently had the opportunity to examine a pancreas prophylactically removed from a patient with a strong family history of pancreatic carcinoma. This gave us the unique opportunity to study the early events in the development of familial adenocarcinoma of the pancreas. Histopathological examination of the pancreas revealed multifocal papillary and nonpapillary mucinous duct hyperplasia. Seven of these foci were microdissected and analyzed for K-ras and p53 mutations. The K-ras mutations were detected by combined mutant-enriched polymerase chain reaction-restriction fragment length polymorphism analysis and characterized further by allele-specific oligonucleotide hybridization. Five of the seven duct lesions harbored activating point mutations in codon 12 of K-ras; a G to A transition was found in four and a G to C transversion in one. In contrast, these lesions did not harbor detectable p53 mutations as determined by denaturing gradient gel electrophoresis of exons 5 to 8, nor was there overexpression of the p53 protein as determined by immunohistochemistry. These findings suggest that mutations in K-ras represent an early event in the pathogenesis of pancreatic carcinoma. In addition, monitoring of patients with a strong family history of pancreatic carcinoma for K-ras mutations may identify patients at risk for the development of invasive carcinoma.
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PMID:Detection of K-ras mutations in mucinous pancreatic duct hyperplasia from a patient with a family history of pancreatic carcinoma. 799 57

In all normal cells, two type of genes, oncogenes and anti-oncogenes, are expressed and control cell proliferation and differentiation. Cell growth is stimulated by oncogenes and inhibited by anti-oncogenes. Cancerization involves loss of control due to defective gene expression either by overexpression of a normal protein (loss of quantitative control) or expression of an abnormal protein (loss of qualitative control). Several oncogenes have been identified. They include three oncogenes, c-myc, N-myc and L-myc, known to be overexpressed in small-cell carcinomas of the lung. Point mutations of the oncogene K-ras is found in 15 to 30% of adenoma carcinomas, especially in smokers. Loss of anti-oncogene function has also been described in processes leading to lung cancer. Chromosome abnormalities, for example the 3p14-23 deletion described in 1982, are found in 100% of small-cell carcinomas and in 50% of non-small-cell carcinomas. This deletion is never found in normal tissue. The gene involved has not yet been cloned. Other mutations or deletions include the RB gene, necessary for neuroendocrine differentiation, and the p53 gene which has undergone mutation in 50% of the non-small-cell carcinomas and 70% of the small-cell carcinomas. These acquired mutations are strongly associated with tobacco smoking. Oncogenes and anti-oncogenes play an important role in the complex step-wise process leading to cancerization. As tumour characterization becomes more precise and precancerous states better controlled, future treatments may relief on inhibiting tumoural growth by using drugs which would substitute for the lost effect of anti-oncogenes or inhibit activation of an oncogene. But at the present time, it is still difficult to define criteria predicting high risk of postoperative relapse or resistance and further studies investigating the correlation between genetic abnormalities and clinical staging and survival curves are required.
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PMID:[Oncogenes and anti-oncogenes in lung cancer]. 820 81


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