Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-seven cases of inflammatory breast cancer were screened for the presence of the p53 protein by immunocytochemical methods using a monoclonal antibody directed against the p53 protein. Three groups were detected: 8 cases (30%) had high levels of p53 in the nucleus of the cancer cells; 9 cases (33%) had a complete lack of detectable staining; 10 cases (37%) showed a pattern of cytoplasmic staining with nuclear sparing. Nucleotide sequence analysis of p53 cDNAs derived from the samples with cytoplasmic staining revealed only wild-type p53 alleles in 6 out of 7 cases. An eighth case was determined to be wild type by a single-strand conformation polymorphism. In contrast, the samples containing nuclear p53 contained a variety of missense mutations and a nonsense mutation. The p53 cDNAs from 3 of the tumors that lacked detectable p53 staining were analyzed, and all 3 had wild-type nucleotide sequences. Interestingly, a case of normal lactating breast tissue also showed intense cytoplasmic staining for p53 with nuclear sparing. These data suggest that some breast cancers that contain the wild-type form of p53 protein may inactivate its tumor-suppressing activity by sequestering this protein in the cytoplasm, away from its site of action in the cell nucleus. The detection of cytoplasmic p53 in normal lactating breast tissue could suggest that this is the mechanism employed in specific physiological situations to permit transient cell proliferation. This observation could explain how some breast cancer tissues inactivate p53 function without mutation.
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PMID:Two distinct mechanisms alter p53 in breast cancer: mutation and nuclear exclusion. 135 91

Gene amplification occurs at high frequency in transformed cells (10(-3)-10(-5)), but is undetectable in normal diploid fibroblasts (less than 10(-9)). This study examines whether alterations of one or both p53 alleles were sufficient to allow gene amplification to occur. Cells retaining one wild-type p53 allele mimicked the behavior of primary diploid cells: they arrested growth in the presence of drug and failed to demonstrate amplification. Cells losing the second p53 allele failed to arrest when placed in drug and displayed the ability to amplify at a high frequency. Thus, loss of wild-type p53 may lead to amplification, possibly caused by changes in cell cycle progression. Other determinants can by-pass this p53 function, however, since tumor cells with wild-type p53 have the ability to amplify genes.
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PMID:Altered cell cycle arrest and gene amplification potential accompany loss of wild-type p53. 135 76

Rat hepatocellular carcinomas (HCCs) induced by aflatoxin B1 (AFB) treatment were examined for changes in the p53 tumor suppressor gene and in p53 suppressor gene expression. A high proportion of HCCs (nine of 11 tumors in six of eight animals) exhibited new p53 restriction fragments, indicating genomic alterations of one of the p53 alleles. Each tumor with an altered p53 restriction-fragment pattern exhibited a new fragment in one of two size classes (3 kb or 7 kb with EcoRI digestion) that were missing portions of the 3' end of the p53 gene. These findings indicate that apparently similar genomic rearrangements or deletions occurred independently in AFB-induced tumors. When compared with nontumor liver tissue from the same animal, the tumors with p53 gene alterations showed dramatically reduced levels of p53 mRNA and protein and greatly increased levels of histone H2B and retinoblastoma tumor suppressor (Rb) mRNA. In two HCCs showing no evidence of p53 restriction-fragment alterations, mutant p53 protein was detected. Mutant protein was also detected in two liver samples containing an adenoma and altered foci. These data suggest that alterations of the p53 tumor suppressor gene are involved in the induction of rat HCC by AFB.
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PMID:Alterations in the structural gene and the expression of p53 in rat liver tumors induced by aflatoxin B1. 135 44

Receptor status, proliferative activity, loss of differentiation, inactivation of tumor suppressor genes, and overexpression of oncogenes are related events that may affect the prognosis of patients with breast cancer. Ninety-seven unselected breast carcinomas were immunostained for estrogen and progesterone receptors, Ki-67 proliferation-associated antigen, p53 tumor suppressor gene product (p53), and c-erbB-2 protein. Immunohistochemical results and clinical data were compared. Altered p53 expression (regarded as indirect indication of inactivating gene alterations) was found in 25.8% of cases and was associated with a high Ki-67 labeling index, high mitotic count, and high histologic grade, with c-erbB-2 overexpression, and with negative estrogen and progesterone receptor status. p53 immunostaining could be found also in cytologic samples and correlated with p53 immunoreactivity on frozen sections of the corresponding tumors. c-erbB-2 protein overexpression was seen in 24.7% of cases and was associated with p53 altered expression and negative receptor status. Double immunohistochemical staining showed p53 and c-erbB-2 immunoreactivity in the same cells. Median and mean +/- standard deviation Ki-67 labeling index values were 15 and 16.32 +/- 10.05, respectively. Ki-67 labeling index was correlated with high mitotic count and was positively associated with histologic grade, negative progesterone receptor status, and p53 expression. Estrogen receptor status was not associated with any histologic or clinical parameters, whereas progesterone receptor status was associated with grading. The direct relation of p53 protein alterations with c-erbB-2 overexpression may be interpreted in light of the multistep model of tumor progression. Cases with altered expression of both p53 and c-erbB-2 proteins could be interpreted as having lost one inhibitory control mechanism of cell proliferation and having gained one activator of the malignant potential. However, in comparing cases with the p53 + c-erbB-2 + phenotype with cases showing positivity for only one of these gene products, no association with higher stages was seen. Detection of p53 altered expression on cytologic samples of malignant tumors may have diagnostic relevance, and p53 immunostaining may prove to be an additional diagnostic criterion in cytologic diagnosis.
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PMID:p53 and c-erbB-2 protein expression in breast carcinomas. An immunohistochemical study including correlations with receptor status, proliferation markers, and clinical stage in human breast cancer. 135 56

Genetic alterations of various cancers have been clarified by recent development of molecular biology. Multiple genetic alterations occur through the development of cancer. Both activation of proto-oncogenes and inactivation of tumor suppressor genes are important for the development of cancer. Alterations of oncogenes such as K-ras, c-erbB-2/HER-2/neu and c-myc, and those of tumor suppressor genes such as p53, RB and DCC have been reported in ovarian cancer. Allelic losses of the specific chromosomes, which suggest the existence of tumor suppressor genes on those chromosomes, also have been reported in ovarian cancer. Further studies on genetic alterations of ovarian cancer will clarify the mechanisms for the development of ovarian cancer and also will develop new methods for prevention, diagnosis and treatment in clinical.
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PMID:[Genetic alterations in the genesis and development of ovarian cancer]. 135 31

Molecular analysis of malignant astrocytomas demonstrated three distinct groups of tumors with chromosome 17p abnormalities, which include (a) deletion of the p53 locus (17p13.1) and mutations in the remaining allele, (b) deletion of the p53 locus but no detectable mutations in the remaining allele, and (c) deletions not including the p53 locus but mutations in one of the alleles. Furthermore, deletion mapping analysis demonstrated allelic loss of genes distal to D17S28/D17S5 markers (17p13.3) in group C tumors. The loss of heterozygosity of genes on chromosome 17 without detectable mutation (group B) or deletion (group C) in the p53 gene implies the presence of a second tumor suppressor gene in the telomeric region of 17p, the homozygous functional inactivation of which may play a role, either alone or in conjunction with p53, in the initiation and/or progression of astrocytic neoplasms.
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PMID:Evidence for the involvement of a potential second tumor suppressor gene on chromosome 17 distinct from p53 in malignant astrocytomas. 135 38

Neoplastic progression in patients with chronic ulcerative colitis (UC) is characterized by the development of epithelial dysplasia, which is accompanied by genetic abnormalities that can be detected by flow cytometric and molecular biologic methods. Distribution of and correlation between histologic abnormalities, DNA content, and loss of heterozygosity for a p53 allele (p53 LOH) in the colons of nine UC patients were analyzed. Loss of a p53 allele was found in 85% (22/26) of biopsy specimens classified histologically as carcinoma, 63% (25/40) of biopsy specimens with high grade dysplasia, and 33% (7/21) of biopsy specimens with low grade dysplasia. Loss of heterozygosity for p53 was also found in 9% (5/57) of biopsy specimens indefinite for dysplasia and in 1/18 biopsy specimens negative for dysplasia, showing that this genetic change may occur early in the histological progression towards carcinoma. Aneuploid DNA contents were more common than p53 LOH in regions with negative, indefinite or low grade dysplastic histology; moreover, p53 LOH was detected only in aneuploid cells and not in diploid epithelium. Aneuploidy alone was not as specific a marker for the concomitant presence of dysplasia or carcinoma in a biopsy sample as aneuploidy combined with p53 LOH. These findings show that aneuploidy may precede both p53 LOH and epithelial dysplasia. Two UC patients' colons contained geographically separated clones of cells with different aneuploidies that also showed loss of different p53 alleles, suggesting that neoplasia may arise within different populations of cells in separate areas of the same colon.
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PMID:Neoplastic progression in ulcerative colitis: histology, DNA content, and loss of a p53 allele. 850 Jul 56

Immunolocalization of the nuclear protein p53 tumor suppressor gene product is considered to be one of the best methods of detecting a mutated form of p53. We have studied p53 immunohistochemically by using monoclonal antibody pAb1801 in 15 cases of esophageal squamous cell carcinoma. Immunoreactive p53 was observed in the nuclei of tumor cells in 4% paraformaldehyde-fixed, frozen sections (12 of 15) and paraffin-embedded sections (11 of 15), but not in routinely processed (10% formalin-fixed) specimens. p53 expression was closely correlated with the malignant phenotype, including dysplasia. p53 was not observed in histologically normal mucosa, except in three cases in which scattered immunoreactivity was observed in parabasal and basal cells. Immunostaining of ki67 and proliferating cellular nuclear antigen on adjacent tissue sections revealed that p53 expression was strongly correlated with ki67 and proliferating cellular nuclear antigen in carcinoma and dysplastic cells, but not in normal mucosa, suggesting involvement of the mutated form of p53 in the cell cycle of malignant cells. Immunohistochemical patterns of p53 were not related significantly to clinicopathologic parameters in the cases examined. Therefore, p53 expression was strongly associated with the proliferation of carcinoma cells but not with that of normal cells in esophageal carcinoma.
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PMID:Expression of p53 in human esophageal carcinoma: an immunohistochemical study with correlation to proliferating cell nuclear antigen expression. 135 81

Changes in the tumor-suppressor gene p53 are frequently acquired during the course of malignant development of human tumors. Recently, constitutional heterozygous mutations in p53 exon 7 have been identified as the primary cause of cancer predisposition in cases of the familial Li-Fraumeni cancer syndrome. These findings underline the need for extensive mutation screening in families with high cancer incidence. This report describes the detection and follow-up by two-dimensional single-strand conformation polymorphism analysis (2DSSCP) of a new germline mutation of p53 exon 8 in a case of suspected Li-Fraumeni syndrome. Although a high cancer incidence had been reported in the family history of the father of siblings suffering from brain tumor and rhabdomyosarcoma, a constitutional heterozygous p53 mutation was identified only in the affected children. Retrospective analysis of archival tissue of a half-sister who died several years ago from a tumor of previously uncertain diagnosis revealed the same mutation. The mutation had therefore occurred in the germ cells of the mother, who thus appears to be a mosaic. The cancer predisposition of the paternal ancestors must have been due to other factors.
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PMID:p53 mosaicism with an exon 8 germline mutation in the founder of a cancer-prone pedigree. 135 93

Two RB fibroblastic strains from patients with hereditary retinoblastoma (RB), namely, RB80F/250R and RB110F, were transfected with plasmid DNAs encoding SV-40 large T-antigen at passage 31 and 10, respectively, These transfected fibroblasts developed into two immortalized cell lines. RB80F/250R/ori- and RB110F/gpt. RB110F/gpt had a similar doubling time as the parental cells, whereas RB80F/250R/ori- grew more rapidly with a doubling time of 19 hours compared to the parental cells which had a doubling time of 50 hours. The RB80F/250R/ori- cell line was particularly interesting cytogenetically since no normal chromosome 13 was present, although a marker chromosome 13 was found. In contrast, two apparently normal chromosome 13s were present in RB110F/gpt cells, but these cells had a marker chromosome which involved chromosome 14 (14 p+). Both the cell lines also had an abnormal chromosome 1 (1q-). RFLP analysis using the chromosome 13 specific VNTR probe, pTH162, assigned to 13q14.1 showed that the DNA from the RB80F/250R/ori- cells contained only a 6.1kb allelic fragment whereas the DNAs from parental RB80F/250R and RB80F cultures demonstrated both the polymorphic 8.0kb and 6.1kb allelic fragments. However, the RB gene per se was normal at the DNA level. Both cell lines expressed SV-40 large T-antigen together with elevated levels of p53 protein. In addition, levels of RB protein were the same in exponentially growing nontransformed parental cell strains and their immortalized cell lines. However, at confluency the levels of RB protein were greatly reduced in nontransformed cells but not in immortalized cell lines under similar conditions. In future studies using these immortalized cell lines, we shall make an attempt to discern the role of the RB gene and other tumor suppressor genes in the regulation of normal and malignant growth.
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PMID:Immortalization of fibroblasts from two patients with hereditary retinoblastoma. 135 29


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