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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Molecular and cell biologic studies of a large number of lung cancer cell lines of all histologic types have revealed several mechanisms active in the pathogenesis of these cells. Small cell lung cancer (also called "oat cell" lung cancer) has a deletion involving chromosome region 3p(14-23) that is confirmed by DNA restriction fragment length polymorphisms analysis (studies done in collaboration with Dr. Susan Naylor). Several lung cancers of both small cell and non-small cell type (including adeno- and squamous cell lung cancer) express the proto-oncogenes c-, N-, or L-myc, and in some cases more than one of these family members. N-myc appears restricted in its expression to the small cell lung cancer type while c-myc and L-myc can be expressed in both small cell and non-small cell lung cancers. Many lung cancers of all histologic types also express large amounts of p53, which are not correlated with the amount or type of myc gene product expressed. In small cell lung cancer, high levels of myc gene expression are usually associated with gene amplification, and not uncommonly there is rearrangement of some of the amplified copies. In non-small cell lung cancer, expression without amplification or rearrangement of myc genes is seen. In contrast, high level expression of p53 is not associated with gene amplification in any lung cancer type. In addition, to these proto-oncogenes acting at a presumed nuclear locus, there is increased expression of various ras family members and the c-raf-1 proto-oncogene (in collaboration with Dr. Ulf Rapp). Lung cancer cells in tissue culture can grow in medium without serum and few or no other growth factors added. Thus, it appears that lung cancer cells can produce their own growth factors which can act in an "autocrine" fashion. The best characterized example of this is gastrin releasing peptide (GRP, also called bombesin) produced by small cell lung cancer. In at least some small cell lung cancers, interference with GRP action by specific monoclonal antibodies results in inhibition of tumor cell growth in culture and in nude mouse xenografts. Thus, constitutively expressed GRP gene may function as a cellular oncogene under certain circumstances in small cell lung cancer. Based on these observations we are proposing to test monoclonal anti-GRP antibodies in patients.
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PMID:Chromosomal deletion, gene amplification, alternative processing, and autocrine growth factor production in the pathogenesis of human lung cancer. 333 4

P53 expression was studied using immunohistochemistry in patients (n=94) with pathologic stage I squamous cell lung cancer treated surgically between 1991-1992. The overall p53 positivity ratio was 48/94. 83 of the cases proved to be suitable for follow-up analysis carried out in November, 1995. 46/83 were p53 positive, and 25/46 patients were alive at the time of analysis. The patients who died (21/46) had a mean survival time of 17.5 months. In p53 negative cases (37/83), however, 29/37 patients were still alive at the time of follow-up, and 8/37 had died with a mean survival time of 23.1 months. A significant correlation could be found between p53 immunopositivity and reduced survival time (p=0.0125). Interestingly, out of 83 cases analyzed histologic evidence of tuberculous scar tissue was present in 9 tumors with a p53 positivity ratio of only 1/9. When flow cytometry was used to examine tumor samples from all subgroups mentioned above (n=32), no correlation was found between the p53 immunopositivity or the prognosis and the DNA content of tumor tissues. Our results suggest that in the early stage of squamous cell lung cancer the p53 positivity may be an indicator of a more aggressive tumor behavior and a shortened survival time.
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PMID:P53 expression in stage I squamous cell lung cancer. 955 14

Lung cancer is the leading cause of cancer death in Taiwan. Potential molecular markers associated with cancer susceptibility and prognosis are the genes involved in tumorigenesis. Therefore, we investigated the association of p53 codon 72 polymorphism with prognosis in 114 lung cancer patients. The estimated median survival times for patients with proline (Pro)/Pro, arginine (Arg)/Arg, and Arg/Pro genotypes were 25, 26 and 36 months, respectively. We also found that patients with the Pro/Pro genotype had a worse prognosis compared with those with Arg/Pro genotypes, especially for patients with squamous cell lung cancer (P = 0.013), male patients (P = 0.028) and those aged 60-69 years (P = 0.052). In patients with early stage lung cancer, patients with Pro/Pro and Arg/Arg genotypes had a tendency for a worse prognosis than those with the Arg/Pro genotype (P = 0.057). Our data suggest that p53 codon 72 polymorphism may be a potential prognostic factor in certain sub groups of lung cancer patients in Taiwan.
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PMID:Prognostic significance of p53 codon 72 polymorphism in lung carcinomas. 1044 64

Smoking prevention will decrease lung cancer incidence in time. However, early detection would improve lung cancer prognosis in subjects at risk provided that specific markers could be identified. We previously reported that retinoic acid receptor (RAR) and retinoid X receptor (RXR) expression was altered in lung tumors. RAR-beta gene status could be derived from corresponding allelotyping and immunohistochemistry data. We now report the continued study on lung cancer precursor lesions. Fluorescence PCR-based assays were used for allelotyping at the RAR/RXR loci of: (a) 66 lung precursor lesions found at the free resection margins of 41 patients undergoing surgery for lung cancer (+ 31 paired tumors); and (b) bronchial cells also found at the free resection margins from 16 current and 8 never smokers operated on for noncancerous diseases. Three microsatellites located at 3p14-21 and 9p21 were also used for interwork comparison. Immunohistochemistry was additionally performed to evaluate P53 and RAR-beta expression in precursor lesions. Chi2 tests showed significant differences (P < 0.05) when comparing the results obtained from never smokers, smokers, squamous metaplasia, dysplasia + in situ carcinoma, and tumors. Microsatellite changes occurred frequently in all samples, but without specificity for any group (P < 0.08-0.52). They were globally correlated with tobacco exposure (P < 0.04), for which the RAR-gamma marker appeared as a preferential target (P < 0.004). Few reparation error phenotypes were observed, mostly at the RXR-alpha and RXR-gamma markers for which combined changes were also linearly increasing from never smokers to dysplasia + in situ carcinoma (P < 0.05 and P < 0.03). RAR-beta marker losses also increased from the first to the last group studied (P < 0.01), with a concomitant decrease in RAR-beta protein expression and correlated p53 increased immunoreactivity (P < 0.02). Losses at 3p14, 3p21, and P16 were frequent, but no significant differences between groups could be found. Unexpectedly, high constitutive homozygosity was observed near the RAR-alpha locus in squamous cell lung cancer cases. RARs/RXRs form homodimers or heterodimers involved in ligand binding. Their added alterations could result in a state of functional vitamin A deficiency in the affected bronchial cells. Further deletion events drawn from a limited repertoire of specific regions such as 3p14-21 and 9p21 could subsequently drive the deficient cells to invasive carcinoma.
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PMID:Retinoic acid receptor and retinoid X receptor alterations in lung cancer precursor lesions. 1085 Apr 30

p53 protein is a critical regulator of the cell cycle and apoptosis and its levels and functions change in response to many stimuli. To assess whether the cytotoxic drugs induce DNA changes, affect phosphorylation and stability of p53 protein, we determined poly-ADP-ribose levels, the expression of p53 protein and its carboxyl-terminal Ser-392 phosphate levels in fiberoptic bronchoscopy biopsy samples taken from patients suffering from recurrent squamous cell lung cancer before and after radiotherapy and chemotherapy. All 14 patients included in this study were in IA-IIIA clinical stage prior to surgery. Radiation/chemotherapy decreased G2/M cell numbers but increased S-phase cells by almost 50% compared to ploidy status before therapy, while median p53 expression was doubled (109% increase). p53 phosphorylated on Ser-392 was also increased by approximately 70% in patients treated with radiotherapy and with chemotherapy and correlated with elevated poly-ADP-ribose levels. Our data suggest that apart from changes in p53 quantity, posttranslational phosphorylation/dephosphorylation-mediated alterations may play an important role in neoplastic cell proliferation as well as in antiproliferative activity of drugs inducing DNA damage and apoptosis.
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PMID:Therapy increases poly-ADP-ribose and p53-Ser392-P levels in recurrent squamous cell lung cancer. 1293 39

Functional regulation of p53 protein, a critical regulator of cell cycle and apoptosis, was investigated in fiberoptic bronchoscopy biopsy samples taken from 23 patients suffering from recurrent squamous cell lung cancer by analyzing the expression and phosphorylation status of the p53 at Ser15 and Ser20 before and after treatment with radiotherapy/cisplatin/vinorelbine. Poly(ADP-ribose) levels as a marker of cellular DNA damage, expression of wild-type and mutated p53 protein, and Ki-67 expression as a marker of proliferation was also determined. Median p53 expression increased (61% increase) after therapy. p53 phosphorylated on Ser20 was also increased by approximately 57% in radiotherapy/chemotherapy patients, and these changes correlated with Ki-67 proliferation and with elevated (by 69%; P < 0.01) poly(ADP-ribose) levels. Our data indicate that apart from changes in p53 quantity, post-translational phosphorylation/dephosphorylation-mediated alterations, especially at Ser20 may play a role in p53 stabilization and, therefore, in antiproliferative activity of drugs inducing DNA damage and apoptosis.
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PMID:p53 N-terminal Ser-15 approximately P and Ser-20 approximately P levels in squamous cell lung cancer after radio/chemotherapy. 1452 25

Genetic alterations at chromosome arm 8p are associated with advanced disease and poor patient outcome in several types of malignant tumors. We studied the frequency of microsatellite instability (MSI) and loss of heterozygosity (LOH) at chromosome 8p in early stage non-small cell lung cancer (NSCLC) of 47 patients with stage I or II disease (25 squamous cell carcinomas and 22 adenocarcinomas). Microsatellite analysis was performed after laser microdissection using 5 polymorphic tetranucleotide microsatellite markers and 4 dinucleotide markers at chromosome 8p. A pentanucleotide repeat marker at the chromosomal locus 17p13.1 (TP53.Alu) was also analyzed. Expression of the mismatch repair (MMR) proteins hMSH2, hMSH6 and hMLH1 was evaluated by immunohistochemistry. Microsatellite instability (MSI) in at least 2 markers was detected in 9 of 47 patients (19.1%) and was predominantly found at tetranucleotide repeats. Sixteen of 47 (34.0%) NSCLC demonstrated LOH at chromosome 8p. All MSI-positive tumors showed normal expression of the MMR proteins. The presence of MSI at chromosome 8p was associated with lymph node metastasis (p=0.02), squamous differentiation (8/25; 32%-p=0.03), and the presence of LOH at the p53 locus (p=0.06). None of the other investigated clinical, pathologic or molecular factors correlated with MSI. Our study showed that an elevated MSI at selected tetranucleotide sequences (EMAST) on chromosome 8p is frequent in early stage squamous cell carcinomas of the lung with lymphatic spread. The tetranucleotide marker panel used in this study was able to indicate lymph node metastasis and high risk disease in patients with resectable squamous cell lung cancer.
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PMID:Microsatellite instability at chromosome 8p in non-small cell lung cancer is associated with lymph node metastasis and squamous differentiation. 1453 77

Lung cancer is the leading cause of death worldwide. High mortality comes out mainly of the fact that majority of the cases are diagnosed in advanced stadium. An expanded diagnostics of precancerous conditions would certainly contribute to lowering the mortality rate. Many of the molecular changes accompanying the multistep cancer development could be observed using the immunohistochemistry method. In this paper we describe the morphology and cell cycle proteins immunoexpression of the novel probable preinvasive lesion - bronchiolar columnar cell dysplasia (BCCD). Thirty cases of BCCD selected out of 193 patients population, treated for primary non-small cell lung cancer were investigated. Loss of P16INK4a protein was observed in 70% of all cases and was statistically significant in patients with adenocarcinoma. Two cases show abnormal cytoplasmic localization of this protein. TP53 protein accumulates in 26.7% of all BCCD. Rb protein was active in 48.3% of the BCCD cases. In two cases we observed differentiation of the cells composing BCCD into multilayer epithelium of the squamous type, which occurs with formation of desmosomes. We suppose that BCCD may be preneoplastic lesion leading to adenocarcinoma as well as to peripheral squamous cell lung cancer.
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PMID:Immunoexpression of P16INK4a, Rb and TP53 proteins in bronchiolar columnar cell dysplasia (BCCD) in lungs resected due to primary non-small cell lung cancer. 1829 70

An immunological study was carried out in 127 cases of surgical treatment of squamous cell lung cancer. Cryostat sections were used to identify markers of proliferation (Ki-67 and topoisomerase IIalpha), apoptosis (p53 and CAS) and intercellular adhesion (E-cadcherin). It was shown that Ki-67 and topoisomerase IIalpha proliferation rates and CAS expression may be interpreted as additional factors of squamous cell cancer aggressiveness while E-cadcherin expression--as a favorable prognosticator. In cases of Ki-67 in excess of 36%, 5-year survival dropped to 38% as compared with 70% when that index was below 36%.
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PMID:[Evaluation of malignancy of squamous cell lung cancer by clinico-morphological, immunohistochemical and prognostic study of tumor markers]. 2021 19

To examine the p53 expression in cancer development, we studied the case of a 59-year-old male suffering from squamous cell lung cancer. He was submitted to surgery for resection of the tumoral mass. Through immunoblot and immunohistochemical analysis, the tumor fragment was shown to bear p53 and hsp70 accumulation not detected in the normal lung tissue sample. Six months later, immunohistochemical analysis of a biopsy sample taken from the previous tumor site showed p53 accumulation. Considering the high specificity for p53 detection (100%), this result suggests probable tumor reincidence, not detected by the ordinary H&E staining.
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PMID:p53 as tumor marker for the early detection of reincidence in lung cancer. 2159 65


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