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)

We have analyzed p53 gene alterations in five cervical cancer derived cell lines. Two of the five cervical cancer cell lines, HTB31 (C-33A) and 32 (HT-3), harbored missense mutations in codons 273 and 245 respectively, whereas the other three tumor cell lines, HTB33 (ME180), 34 (MS751) and 35 (SIHA), did not reveal any mutation in the p53 coding sequence spanning codons 126-307. Although all the tumor cell lines express comparable levels of p53 RNA, only HTB31 and HTB32 contain high or detectable levels respectively of p53 protein. The other three tumor cell lines, where neither p53 mutation nor the expression of p53 protein could be detected, were found to harbor human papilloma virus (HPV) 16 or 18. The inactivation of the wild-type p53 function resulting from a missense mutation, or the lack of detectable wild-type p53 protein due to the translational/post-translational deregulation of p53 protein levels may be the contributing factor in the tumorigenicity of these five cases of cervical cancer. The lack of detectable p53 protein in HTB33, 34 and 35 associates with the presence of either HPV16 or -18 in these cell lines.
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PMID:The status of the p53 gene in human papilloma virus positive or negative cervical carcinoma cell lines. 132 52

The RB and p53 tumour suppressor genes encode nuclear proteins that exert an inhibitive effect on cell growth. A large variety of human tumour types manifest loss or mutation of the RB or p53 genes, and p53 mutation is the commonest genetic alteration found in tumour cells. In addition, the RB and p53 proteins may be inactivated by complex formation with viral oncoproteins--for instance, in the case of cervical carcinoma carrying human papilloma virus. In vivo introduction of an intact RB or p53 gene into malignant cells lacking the respective gene results in suppression of the neoplastic phenotype and thus of tumourigenicity, p53 being the more potent of the two in this respect. Further elucidation of tumour suppressor genes may well result in future improvement in the diagnosis and treatment of cancer.
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PMID:[Tumor suppressor genes: mutations in RB and p53 genes are significant carcinogenic factors]. 140 28

To study the oncogenesis of human esophageal carcinoma, the presence of DNA sequences homologous to several DNA tumor viruses and the expression of oncogenes and growth factor genes were examined in two esophageal carcinoma cell lines of Chinese origin, CE48T/VGH and CE81T/VGH. Southern blot analyses failed to detect sequences homologous to hepatitis B virus (HBV), Epstein-Barr virus (EBV), herpes simplex virus type 2 (HSV-2), cytomegalovirus (CMV) or human papilloma virus (HPV) genomes. Northern blot analyses revealed that c-myc, c-src, c-H-ras, c-abl, c-sis, and p53 genes were expressed. In addition, transcripts of transforming growth factor alpha (TGF alpha), TGF beta, and platelet derived growth factor A (PDGF A) genes were detected. These studies suggest that DNA tumor viruses may not be involved in the carcinogenesis of esophageal carcinoma. However, cooperation among different oncogenes and the production of growth factors may play an important role in that carcinogenesis.
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PMID:Absence of genomes of DNA tumor viruses and expression of oncogenes and growth factors in two esophageal carcinoma cell lines of Chinese origin. 147 73

In animal systems, complete and permanent eradication of tumours can be achieved by adoptive transfer of MHC-restricted T cells, combined with IL2. In certain types of human cancer (melanoma and perhaps renal cell carcinoma), tumour-specific T cells are probably the therapeutically most active cells among LAK or TIL cells. To prove these points, it is necessary to conduct trials with cloned tumour-specific T cells. Other potentially immunogenic tumors are cervical carcinoma, associated with human papilloma virus, and Burkitt's lymphoma, associated with Epstein-Barr virus. Most other human tumours, caused by subtle mutations in proto-oncogenes, are likely to be poorly or non-immunogenic. It is worthwhile trying to overcome this by vaccination with IL2 or IFN gamma-producing tumour cells or by deliberate vaccination with desirable targets for tumour-specific CTL such as the products of point-mutated oncogenes, including ras (Jung and Schleusener, 1991) and p53 (Rodriguez et al., 1990; Halevy et al., 1990), provided the relevant peptides are processed and bound to MHC class I molecules. Other potential targets are breakpoint peptides of translocated oncogene products such as bcr/abl (Van Denderen et al., 1990). In viral systems, it has already been established that peptide vaccination for protective CTL induction is feasible (Aichele et al., 1989; Schulz et al., 1991; Kast et al., 1991).
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PMID:T-cell immunotherapy of cancer. 175 15

A novel class of oncogene has been recognised whose loss-of-function results in the expression of the malignant phenotype. Two examples of such genes are the human retinoblastoma predisposition gene (RB1) and the gene encoding the cellular protein p53. These genes are thought to regulate and limit normal proliferation of cells and, as a consequence, can suppress tumorigenicity when introduced into transformed cells. They are hence frequently described as 'tumour suppressor genes'. Both RB1 and p53 gene products are bound by various transforming early proteins encoded by the DNA tumour viruses SV40, adenovirus and human papilloma virus. It is thought that they are thus sequestered and rendered inactive. Thus, a coherent model is emerging whereby inactivation, either by mutation of sequestration, of these tumour suppressor genes may contribute to natural and experimental carcinogenic processes.
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PMID:The nuclear oncoproteins: RB and p53. 215 36

Tumor suppressor p53 is a transcription activator that upregulates target genes containing the p53 binding site. UREB1, a DNA binding protein that is tyrosine phosphorylated in vivo, shares a significant homology with the human papilloma virus E6 associated protein (E6-AP). E6-AP forms a ternary complex with E6 and p53 and participates in the ubiquitination of p53. Based on the homology with E6-AP, but taking into account the nuclear localization of UREB1 and its smaller size, the present study used a transient transfection system to examine whether UREB1 influenced p53-stimulated transcription. Co-transfection of a vector expressing wildtype UREB1 with one expressing p53 into H1299, a p53 negative cell line, resulted in a pronounced suppression of p53 transactivation. The inhibitory effect was significantly attenuated by mutation of a tyrosine residue in the consensus tyrosine phosphorylation sequence of UREB1. These data suggest that optimal suppression of p53 transactivation requires tyrosine phosphorylated UREB1 and that tyrosine phosphorylation and dephosphorylation processes may be involved in the regulation of p53 transactivation.
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PMID:UREB1, a tyrosine phosphorylated nuclear protein, inhibits p53 transactivation. 747 39

Tumour-infiltrating lymphocytes (TIL) and tumours from six patients with squamous cell carcinomas of the head and neck (SCCHN) were investigated. The six tumours all expressed major histocompatibility complex (MHC) class I antigens both in vivo and as tumor cell lines grown in vitro. In addition, the cancer cells either overexpressed the tumour-suppressor gene product p53 or harboured human papilloma virus 16/18 (HPV). The TIL were expanded in vitro in the presence of interleukin-2, immobilised anti-CD3 mAb and soluble anti-CD28 mAb. Expanded TIL cultures contained both CD4+ and CD8+ T cells, but generally contained few CD56+CD3- cells of the natural killer (NK) phenotype. CD8+ T cells dominated the individual TIL cultures from five of the six patients and showed significant autologous tumour cell lysis. In TIL cultures derived from four of these tumour-reactive TIL cultures, killing could be partially blocked by an anti-MHC class I mAb. TIL cultures reacting with autologous tumour cells also showed strong TCR/CD3-redirected cytotoxicity when assayed against hybridoma cells expressing anti-TCR/CD3 mAb as well as natural-killer(NK)-like activity. A number of TIL cultures devoid of autologous tumour cell lysis were capable of lysing the natural-killer(NK)-sensitive K562 cell line suggesting that the SCCHN cells themselves are resistant to NK-like lysis. In conclusion, TIL cultures from head and neck carcinomas contain T cells which, upon expansion in vitro, can lyse autologous tumour cells in a MHC-class-I-restricted fashion. Thus, the results of the present study document that carcinomas of the head and neck in some patients are infiltrated by cytotoxic T cell precursors potentially capable of rejecting the autologous tumour.
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PMID:Tumour-infiltrating lymphocytes mediate lysis of autologous squamous cell carcinomas of the head and neck. 748 67

Recent in-vitro models of mammary epithelial cell (MEC) immortalization have provided a practical approach to begin to dissect the molecular mechanisms of breast tumorigenesis. Introduction of a single oncogene, the human papilloma virus (HPV)-16 E6, induces efficient and reproducible preneoplastic transformation of normal MECs, by inducing degradation of the tumor suppressor protein p53. The role of p53 has also been demonstrated by analyses of a model of gamma-radiation-induced MEC transformation. Recently, efficient retroviral gene transfer has allowed identification of multiple mammary epithelial cell types that show distinct susceptibilities to HPV E6 and E7 oncogenes, indicating a cell-type-specific predominance of the tumor suppressor proteins p53 and Rb which are targeted by E6 and E7, respectively. Further analyses of these models are likely to elucidate the biochemical mechanisms of early mammary tumorigenesis.
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PMID:Preneoplastic transformation of human mammary epithelial cells. 749 87

Multiple mammary epithelial cell (MEC) types are observed both in mammary ducts in vivo and in primary cultures in vitro; however, the oncogenic potential of different cell types remains unknown. Here, we used human papilloma virus 16 E6 and E7 oncogenes, which target p53 and Rb tumor suppressor proteins, respectively, to immortalize MECs present in early or late passages of human mammary tissue-derived cultures or in milk. One MEC subtype was exclusively immortalized by E6; such cells predominated in late-passage cultures but were rare at early passages and apparently absent in milk. Surprisingly, a second cell type, present only in early-passage tissue-derived cultures, was fully immortalized by E7 alone. A third cell type, observed in tissue-derived cultures and in milk, showed a substantial extension of life span with E7 but eventually senesced. Finally, both E6 and E7 were required to fully immortalize milk-derived MECs and a large proportion of MECs in early-passage tissue-derived cultures, suggesting the presence of another discrete subpopulation. Identification of MECs with distinct susceptibilities to p53- and Rb-targeting human papillomavirus oncogenes raises the possibility that these cells may serve as precursors for different forms of breast cancer.
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PMID:Immortalization of distinct human mammary epithelial cell types by human papilloma virus 16 E6 or E7. 753 74

Leukoplakia has evolved as a clinico-pathologic concept over many years, with the current clinical designation being accepted worldwide. Reflective of the biology of leukoplakia is the concept of cellular atypia and epithelial dysplasia. Adding to a better understanding of leukoplakia in general has been the definition of relevant clinical subsets which, in some cases, includes etiology (snuff), while in other cases a verrucous clinical appearance will suggest a more aggressive anticipated behavior pattern. Tobacco usage, in many of its forms, remains the prime etiologic factor; however, other considerations also apply. More recently, the potential etiologic role of Candida albicans has been stressed, as well as its possible role in carcinogenesis. So-called oral hairy leukoplakia has been defined in relation to a possible Epstein-Barr viral infection, usually in the immunosuppressed patient. Other viruses, human papilloma virus in particular, have been implicated in leukoplakia, while genetic alterations involving tumor suppressor elements (p53) have also been investigated. Finally, the management of this common condition remains a variable and includes local, topical, and systemic therapies such as anti-oxidants, carotenoids, and retinoids.
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PMID:Oral leukoplakia. 754 21


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