Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the frequency of mutations in the p53 gene in human prostate cancer. The investigated material consisted of 20 primary-tumor tissue specimens, obtained by transurethral resection and tissue specimens of 15 lymph-node metastases, obtained at total prostatectomy. The applied methods encompassed immunohistochemistry on frozen sections, using the monoclonal antibody PAb 1801, and single-strand conformation polymorphism (SSCP) analysis, after amplification of single exon sequences by PCR, on exons 5 to 8 of the p53 gene. The mutations, leading to aberrantly migrating bands in the PCR-SSCP analysis, were identified by direct sequencing of the PCR product. Immunohistochemical and PCR-SSCP analysis were completely confirmative. In the primary tumors, mutations were found in 10% of the specimens (codons 232 and 273), and in lymph-node metastases in 15% of the specimens (codons 248 and 273). In one case (codon 273), the same mutation was found both in the primary tumor and in the lymph-node metastasis. Our results show that p53 mutations are infrequent in both primary and metastatic prostate tumors. In addition, they indicate that there is no strict correlation between p53 mutation and tumor metastasis.
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PMID:Frequency and characterization of p53 mutations in primary and metastatic human prostate cancer. 831 37

Inactivation of p53, a tumor suppressor gene, contributes to the genesis and/or progression of a substantial fraction of all human cancers, including > or = 50% of breast, lung, and colon carcinomas. Mutated p53 alleles typically contain missense single-base substitutions within exons 5-8 and encode abnormally stable p53 proteins that accumulate to high levels in tumor cell nuclei. To evaluate the frequency, type, and clinical significance of p53 mutation in human prostate cancer, archival tumor material from 150 prostate cancer patients was examined by immunohistochemistry (IHC) with anti-p53 antibodies. Abnormal nuclear p53 accumulation (IHC) was observed in 19 tumors (12.7%) and was strongly related to disease stage (23% of 69 stage III or IV tumors were IHC+ versus 4% of 74 stage 0-II tumors; P < 0.001, Fisher's exact test). The methods of polymerase chain reaction, single-strand conformational polymorphism, and direct sequencing were used to identify mutations, predominantly missense single-base substitutions in exons 5, 7, or 8 in 9 of 14 IHC+ cases but in none of 20 IHC- cases; 5 of these mutations were G:C-->A:T transitions at CpG dinucleotides. These data indicate that mutated p53 alleles are quite uncommon in early prostate cancers but are found in 20-25% of advanced cancers, suggesting a role for p53 mutation in the progression of at least a subset of prostate cancers.
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PMID:p53 is mutated in a subset of advanced-stage prostate cancers. 832 47

The expression of the mutant p53 tumor suppressor gene was evaluated in 33 human prostate carcinomas. Using an immunohistochemical method with monoclonal antibodies PAb 1801 and PAb 240, 26 (79%) tumors demonstrated positive immunostaining for mutant p53. Only areas of glandular tumor were positive, with adjacent stromal elements and areas of glandular hyperplasia being negative. The predominant staining pattern was cytoplasmic. This pattern may be related to p53 binding to certain heat shock proteins (HSP 72/73), as a monoclonal antibody to these proteins demonstrated a cytoplasmic location as well. These results demonstrate that abnormal p53 expression is a frequent event in prostate cancer.
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PMID:Mutant p53 expression in prostate carcinoma. 842 37

Tumor-suppressor genes (antioncogenes or recessive oncogenes) are cancer genes that achieve their oncogenic effect by mutational inactivation of both normal alleles. By contrast, oncogenes are created from protooncogenes by mutations that lead to aberrant functional activation. Mutation of multiple suppressor genes and/or oncogenes probably is required for the genesis of most human neoplasms. Two well-characterized tumor-suppressor genes, the retinoblastoma gene (rb) on chromosome 13q and p53 on chromosome 17p, frequently are mutated in a broad range of human cancer types. Mutations of these genes have been documented in prostate carcinoma but appear to affect only a subset of cases. Nevertheless, as in other cancers, introduction of normal copies of rb or p53 suppresses the neoplastic properties of prostatic tumor cells carrying mutated alleles of the relevant gene. These results suggest that mutation of rb or p53 is involved in the genesis or progression of some prostate cancers. Frequent allelic losses of certain chromosome arms (especially 8p, 10p and q, and 16q) from prostatic cancer cells may indicate the involvement of novel suppressor genes located in these regions. Although the inactivation of suppressor genes appears to be a common genetic mechanism in human oncogenesis, the rates of mutation of particular genes vary widely with the type of cancer. It is unknown whether prostate cancers with or without mutation of rb, p53, or other suppressor loci differ biologically or prognostically; this is an area of active investigation. Fundamental understanding of the genetic lesions that occur during human oncogenesis has great potential for clinical application in diagnosis, prognosis, and therapy.
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PMID:Recessive oncogenes. 842 41

Incidental prostate cancer is an indolent disease typically characterized by a benign clinical course. This is not clearly established, however, as recent reports suggest that up to 27% of cases progress with long-term follow-up. The indolent history of this disease led initially to the hypothesis that mutations of the p53 gene would be an infrequent event in this patient population. Archival specimens from 24 patients with Stage A1 carcinomas were evaluated for abnormal p53 expression. In 23 patients the disease was diagnosed after transurethral resection for bladder outlet obstructive symptoms, and in one patient after a radical prostatectomy. Using a monoclonal antibody (PAb 240) and an immunohistochemical technique, a total of 36 microfoci of tumor were evaluated. Thirteen (36%) microfoci were positive with an intense nuclear staining pattern (2+), and eight (22%) microfoci had an intermediate staining pattern. Four areas of prostatic intraepithelial neoplasia also stained positively with a 2+ staining pattern. These results suggest that abnormal p53 expression is a feature of a significant number of incidental prostatic carcinomas and that this occurrence is an early event in the development of the malignant phenotype.
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PMID:p53 expression in incidental prostatic cancer. 848 85

Alterations of the p53 gene are among the most frequent genetic lesions in a variety of human malignancies. Their role in prostate cancer is, however, unclear. We have analyzed 10 primary and two metastatic human prostate carcinomas as well as 3 prostate cancer cell lines for mutations of the p53-gene. Using single strand conformational polymorphism analysis (SSCP) and direct sequencing of the polymerase chain reaction (PCR) products, p53 mutations were detected in 1 of 10 primary prostate cancers. By contrast, 1 of 2 metastatic tumors and all 3 prostate cancer cell lines (derived from metastases) were found to contain a mutant p53 gene. Thus, our data suggest that alterations of the p53 gene at the mutational "hot spots" appear to occur infrequently in primary human prostate cancer, but may emerge in later stages of tumor progression. Furthermore, we confirm that loss of heterozygosity at a locus telomeric to p53, but not including p53, is associated with metastatic progression in 1 case.
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PMID:p53 gene alterations in human prostate carcinoma. 851 Feb 67

The progression of prostatic adenocarcinoma from localized disease to metastatic carcinoma appears to be a multi-step sequence. The expression of common oncogenes/oncosuppressor genes and the mediating effect of neuroendocrine tumor cells may play a role in this progression. The expression of the more frequently investigated oncogenes/oncosuppressor genes (p53, c-myc, c-erbB-2, bcl-2) and the presence of neuroendocrine cells were assessed in prostatic cancer tissue from patients with localized and metastatic cancer. These oncogenes/oncosuppressor genes were evaluated according to tumor stage and grade and their relationship to one another. Grade was not related to any of the oncogene markers or to the presence of neuroendocrine cells. Advancing stage was associated with a significant increase in p53 expression, while other markers remained constant in all stages. Neuroendocrine cells, p53, c-myc, c-erbB-2 and bcl-2 were rarely co-expressed at any stage of prostate cancer.
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PMID:Immunohistochemical detection of oncogene proteins and neuroendocrine differentiation in different stages of prostate cancer. 853 88

Japanese breast cancer families were collected and classified into the following 7 types according to the onset age and the distribution of other cancers in the family lines; early-onset type, late-onset type, familial breast-ovarian cancer type, familial breast-prostate cancer type, familial breast-thyroid cancer type, familial male and female breast cancer type and multiple primary cancer type. We have detected no p53 germ line mutations in the patients from these families. Linkage with BRCA1 was not detected in any single families. These data indicate that neither BRCA1 or p53 is a major susceptible gene in Japanese familial breast cancer. However, in the two site-specific breast cancer families, the same nonsense mutation of the BRCA1 gene was detected.
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PMID:[Familial breast cancer]. 853 41

We examined 24 human bladder cancer tissues for possible mutations in the entire coding region of the human DNA polymerase beta gene using polymerase chain reaction analysis, single-strand conformational polymorphism analysis of RNA, and sequence analysis. DNA polymerase beta gene mutations were observed in four of the 24 cases (16.7%) and included three missense point mutations and a single base insertion. The single base insertion was also observed in our previous study of human prostate cancer, suggesting that this region may be a hot spot for mutation of the DNA polymerase beta gene. No clinical or pathological association was found among the four cases that contained the mutation. Three of the four cases with DNA polymerase beta gene mutation had mutations of the p16 or RB genes or loss of heterozygosity of the p53 and APC gene loci. The results of the study presented here suggest that DNA polymerase beta gene mutations, in combination with mutations of tumor suppressor genes, may be involved in certain cases of human bladder cancer.
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PMID:DNA polymerase beta gene mutations in human bladder cancer. 856 64

The RRR-alpha-tocopheryl succinate derivative of vitamin E, referred to as vitamin E succinate (VES), inhibits the proliferation of three metastatic human prostatic cancer cell lines, LNCaP, PC-3, and DU-145. LNCaP is a lymph node-derived androgen-sensitive prostate cell line; these cells are defective for response to transforming growth factor-beta (TGF-beta) but are normal for cell cycle-related tumor suppressor genes: p53 and retinoblastoma (Rb). PC-3 is a bone marrow-derived androgen-insensitive prostate cell line; these cells are defective for both p53 alleles but normal for both Rb alleles. DU-145 is a brain-derived androgen-insensitive prostate cell line; these cells are defective for both p53 and both Rb alleles. VES at 5, 10, and 20 micrograms/ml inhibited DNA synthesis in the three cell lines in a dose-dependent manner. Purified TGF-beta 1 at 1 ng/ml inhibited DNA synthesis of PC-3 cells within 24-72 hours and DU-145 cells at 72 hours but did not inhibit DNA synthesis of LNCaP cells. Previous studies in our laboratory showed that VES growth-inhibited tumor cells secrete biologically active antiproliferative factor TGF-beta s, suggesting that VES's mechanism of growth inhibition may involve the TGF-beta system of growth control.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:RRR-alpha-tocopheryl succinate inhibits the proliferation of human prostatic tumor cells with defective cell cycle/differentiation pathways. 858 52


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