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)

Breast tumors are thought to originate, grow, and metastasize in an environment which includes steroid hormone receptors, their cognate steroid ligands, and many gene products which are regulated by steroid hormone receptor-ligand complexes. In this paper we describe highly sensitive and quantitative immunofluorometric procedures for measuring three proteins that are candidate prognostic indicators in breast cancer, namely, the p53 tumor suppressor gene product, carcinoembryonic antigen (CEA), and prostate specific antigen (PSA). These proteins were quantified in over 950 cytosolic tumor extracts along with estrogen and progesterone receptors (ER, PR). Association analysis between all five biochemical parameters revealed strong negative associations between p53 and receptors and strong positive associations between CEA and receptors. Negative associations between p53 and CEA and between CEA and PSA were also found. These associations, not quantitatively studied in previous reports, are related to each other using a hypothetical model. The observed associations may further contribute to the understanding of the biology of breast tumors.
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PMID:Quantitative analysis of mutant p53 protein in breast tumor cytosols and study of its association with other biochemical prognostic indicators in breast cancer. 752 72

This report describes the development and characterization of an epithelial cell line (BPH-1) from human prostate tissue obtained by transurethral resection. Primary epithelial cell cultures were immortalized with SV40 large T antigen. One of the isolated clones was designated BPH-1. These cells have a cobblestone appearance in monolayer culture and are non-tumorigenic in nude mice following subcutaneous injection or subrenal capsule grafting. They express the SV40 large T antigen and exhibit increased levels of p53, as determined by immunocytochemistry. Cytogenetic analysis by G-banding demonstrated an aneuploid karyotype with a modal chromosome number of 76 (range 71 to 79, n = 28) and 6 to 8 marker chromosomes. Some structurally rearranged chromosomes were observed, but the Y chromosome was normal. The expressed cytokeratin profile was consistent with a prostatic luminal epithelial cell. This profile was the same as that of primary prostatic epithelial cultures from which the BPH-1 cells were derived. In serum-free culture in plastic dishes epidermal growth factor (EGF), transforming growth factor (TGF)-alpha, fibroblast growth factor (FGF) 1 (aFGF), and FGF 7 (KGF) induced increased proliferation in these cells whereas FGF 2 (bFGF), TGF-beta 1, and TGF-beta 2 inhibited proliferative activity. Testosterone had no direct effect on the proliferative rate of BPH-1 cells. 5 alpha-Reductase, 3 alpha-hydroxysteroid oxidoreductase, and 17 beta-hydroxy-steroid oxidoreductase activities were detected in BPH-1 cells. Expression of androgen receptors and the secretory markers, prostate specific antigen and prostatic acid phosphatase, were not detectable by immunocytochemistry, biochemical assay, or RT-PCR analysis.
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PMID:Establishment and characterization of an immortalized but non-transformed human prostate epithelial cell line: BPH-1. 753 34

Markers for cancers in the blood include secreted glycoproteins of solid tissue tumors as well as cell surface markers, and chromosomal rearrangements or mutated genes in circulating blood cells. The most successful markers for the diagnosis of solid tissue cancers have been alphafetoprotein and prostate specific antigen. Other markers, such as CEA and a number of carbohydrate epitopes, e.g., CA 15.3, CA 19.9, CA 50, CA 242, and mucin epitopes, such as MCA, CA 125, and DU-PAN-2 are now being used to determine prognosis and to monitor the response to therapy of a variety of cancers. Cytologic markers in the blood include clusters of differentiation (CD) epitopes on blood cells and chromosomal changes, primarily translocations found in many human lymphomas. In the future more specific mutations in specific oncogenes or alterations in expression of oncogenes or suppressor genes, such as p53, may provide clinically useful markers.
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PMID:Detection of cancer by tumor markers in the blood: a view to the future. 835 41

Primary prostate epithelial and prostate adenocarcinoma cells cultured in serum-free medium grew for up to 10 passages before senescence. Cells from prostate adenocarcinoma of a 55-year-old patient without lymph node involvement were transfected with plasmids containing recombinant human papilloma virus HPV16 or HPV18 DNA and the selectable neomycin-resistance gene. After G-418 selection, cells underwent crisis, and surviving cells infected with retroviruses encoding the HPV18 E6/E7 genes (HPV-PAC1), transfected with a head-to-tail dimer of the complete HPV16 genome (HPV-PAC2), or transfected with HPV18 E6/E7 early genes (HPV-PAC3) were established. HPV-PAC1 and HPV-PAC2 cultures appeared morphologically similar to primary cultures even after 40 passages. However, HPV-PAC2 cultures had a clonal morphology. All lines were positive for cytokeratin 18, had acquired vimentin expression, and contained either HPV16 or HPV18 sequences integrated into host DNA. None was tumorigenic in nude mice or formed colonies in soft agar. These cells did not secrete prostate specific antigen nor respond to androgen although tamoxifen inhibited the growth of the cells. Immunohistochemistry showed no evidence of p53 overexpression. Further characterization of these cell lines and examination of their response to chemotherapeutic agents may provide relevant information for the study of hormone-independent PC.
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PMID:Immortalization of human adult prostatic adenocarcinoma cells by human papilloma virus HPV16 and -18 DNA. 862 Apr 53

Progress in prostate cancer research has been hindered by the lack of well characterized, immortalized, human prostatic epithelial cell lines that express markers of normal prostatic epithelial cells and mimic normal growth and differentiation responses to androgens. The objectives of this study were to: (i) establish immortalized cell lines from non-neoplastic, adult human prostatic epithelium using adenovirus-12/simian virus-40 (Ad12-SV40) hybrid virus; (ii) establish their prostatic epithelial origin; (iii) demonstrate androgen responsiveness; and (iv) examine response to growth factors. Primary epithelial cell cultures derived from a non-neoplastic, adult human prostate were infected with the Ad12-SV40 virus. Several immortalized clones were isolated. Single cell cloning of one clone, free of cytopathic effects, gave rise to the PWr-1E cell line. An immortalized cell line PWR-1E, which expresses many characteristics of normal prostatic epithelial cells was established. Immunostaining showed that cells express cytokeratins 8 and 18 normally expressed by differentiated, secretory prostatic epithelial cells. The most remarkable characteristics of PWR-1E cells are growth stimulation, increased expression of androgen receptor and induction of prostate specific antigen (PSA) expression in response to androgens, which indisputably establish their prostatic epithelial origin. They are positive for SV40 large-T antigen and show strong nuclear staining for p53. Cells from passages 23 and 40 were not tumorigenic in nude mice even when co-injected with Matrigel. They grow in a serum-free defined medium and respond to EGF, bFGF and TGF-beta. Passage 42-cells showed a human male (XY), hyperdiploid karyotype. The PWR-1E cell line is the only known Ad12-SV40-immortalized human prostatic epithelial cell line. PWR-1E cells can be used to study (i) the etiology and the multistep process of carcinogenesis and tumor progression in the human prostate; (ii) normal prostate physiology and differentiation; and (iii) potential prostate cancer chemopreventive agents.
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PMID:Prostate specific antigen and androgen receptor induction and characterization of an immortalized adult human prostatic epithelial cell line. 876 20

In spite of the prevalence of prostatic adenocarcinoma, the development and natural history of this malignancy is poorly understood. This paper reviews the current knowledge of biomarker expression during the development and progression of prostatic adenocarcinoma. Emphasis is placed on the comparison of biomarker expression in benign prostatic epithelium, intraepithelial neoplasia (PIN), a putative preinvasive lesion, and prostatic adenocarcinoma. Within the benign epithelium, the proliferative potential is restricted to the basal cells as demonstrated by the expression of proliferating cellular nuclear antigen (PCNA). The strong expression of the bcl-2 protein, an inhibitor of a apoptosis, supports the concept that the basal cells or a subpopulation of the basal cells represent the stem cell of the epithelium. In addition, the strong expression of growth factor receptors such as the epidermal growth factor receptor (EGFr), p185erbB-2, p180erbB-3, and c-met suggests that the growth of the basal cells is regulated by autocrine or paracrine factors. The luminal cells express secretory products such as prostate specific antigen and prostatic acid phosphatase, but demonstrate little expression of PCNA as well as growth factor receptors and proto-oncogene products. These observations are consistent with the theory that the luminal cell population is derived from the differentiation of the basal cells. In contrast to the normal epithelium, PCNA expression is frequently detected in the dysplastic luminal cells of the PIN lesion. Likewise, strong expression of p185erbB-2, p180erbB-3 and the c-met proto-oncogene product is also detected in the luminal cells of PIN lesions. Other factors which are strongly expressed by the dysplastic luminal cells include the nm23-H1 gene product, tumor associated glycoprotein-72 (TAG-72), fatty acid synthetase (FASE) and proteolytic enzymes. These findings suggest that PIN lesions are derived from an impairment of the differentiation of basal cells. The majority of biomarkers such as PCNA, p185erbB-2, P180erbB-3, TAG-72, nm23-H1 and FASE which are strongly expressed in PIN lesions are also expressed in prostatic adenocarcinoma supporting the concept that PIN is a preinvasive lesion. Mutations of the p53 tumor suppressor gene, as well as strong expression of transforming growth factor alpha and bcl-2 typically occur in advanced stage prostatic adenocarcinomas and therefore likely represent late events in the development of prostatic adenocarcinoma.
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PMID:Changes in biomarker expression in the development of prostatic adenocarcinoma. 915 21

Prostate cancer and benign tumors of the prostate are the two most common neoplastic diseases in men in the United States, however, research on their causes and treatment has been slow because of the difficulty in obtaining fresh samples of human tissue and a lack of well characterized cell lines which exhibit growth and differentiation characteristics of normal prostatic epithelium. Non-neoplastic adult human prostatic epithelial cells from a white male donor were immortalized with human papillomavirus 18 which resulted in the establishment of the RWPE-1 cell line. Cells from the RWPE-1 cell line were further transformed by v-Ki-ras to establish the RWPE-2 cell line. The objectives of this study were to: (1) establish the prostatic epithelial origin and androgen responsiveness of RWPE-1 and RWPE-2 cell lines; (2) examine their response to growth factors; and (3) establish the malignant characteristics of the RWPE-2 cell line. Immunoperoxidase staining showed that both RWPE-1 and RWPE-2 cells express cytokeratins 8 and 18, which are characteristic of luminal prostatic epithelial cells, but they also coexpress basal cell cytokeratins. These cell lines show growth stimulation and prostate specific antigen (PSA) and androgen receptor (AR) expression in response to the synthetic androgen mibolerone, which establishes their prostatic epithelial origin. Both cell lines also show a dose-dependent growth stimulation by EGF and bFGF and growth inhibition when exposed to TGF-beta, however, the transformed RWPE-2 cells are less responsive. RWPE-1 cells neither grow in agar nor form tumors when injected into nude mice with or without Matrigel. However, RWPE-2 cells form colonies in agar and tumors in nude mice. In the in vitro invasion assay, RWPE-1 cells are not invasive whereas RWPE-2 cells are invasive. Nuclear expression of p53 and Rb proteins was heterogeneous but detectable by immunostaining in both cell lines. The RWPE-1 cells, which show many normal cell characteristics, and the malignant RWPE-2 cells, provide useful cell culture models for studies on prostate growth regulation and carcinogenesis.
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PMID:Androgen responsive adult human prostatic epithelial cell lines immortalized by human papillomavirus 18. 921 5

The clinical course of prostate cancer (PCa), the most common cancer in Swedish men, is highly variable and difficult to predict. Consequently, there is an urgent need to distinguish tumours with a high risk of progression from those with a low risk. To investigate the prognostic implications of proliferation and apoptosis, two important processes in tumor biology, immunoreactivity for biomarkers associated with these processes was assessed, quantified in indexes, and related to cause-specific survival (CSS). A consecutive series of 186 men presenting with voiding symptoms and PCa were treated with transurethral resection and deferred endocrine therapy. After 13-21 years follow-up, 43% of these men had died of prostate cancer. In a subgroup of men with localised disease at the time of diagnosis, 27% succumbed to the disease. Immunoreactivity for p53 protein, indicative of a defective p53 function, predicted shorter CSS in univariate (52 vs 123 months, p < 0.0001), but not in multivariate analysis. Mean index for the apoptosis blocking bcl-2 protein was higher in foci of prostatic intraepithelial neoplasia, a putative precursor to PCa, than in manifest cancer areas (79 vs 12, p < 0.0001). This indicates that bcl-2 may be involved in early tumourigenesis. No prognostic value was found for the bcl-2 index. A high index for the proliferation marker Ki-67 predicted shorter CSS in univariate (53 vs 132 months p < 0.0001) and in multivariate analysis. To test if p53 is predictive for clinical radioresistance, as suggested by experimental models, p53 immunoreactivity was investigated in biopsies obtained before radical radiotherapy in an unrelated series of 60 PCa patients. Patients with p53 reactive tumours had longer CSS, indicating that p53 is not treatment-predictive for radiotherapy in Pca. Core biopsies were obtained before and a week after castration therapy in patients with advanced PCa. According to the serum prostate specific antigen (PSA) level 3 months after therapy, 15 responding tumours and 13 non-responding tumours were selected. Regressive morphology was seen in 14/15 responders after castration therapy, compared with 4/13 non-responders. Median apoptotic index increased significantly after castration therapy for responders (from 2.6 to 3.5, p < 0.05) whereas it was 2.8 before and after therapy in non-responders. This indicates that subsequent clinical response can be predicted by the induction of regressive morphology and an increase in apoptotic index. In conclusion, immunoreactivity for Ki-67 appeared to be a putative prognostic factor in PCa, whereas the prognostic value of p53 and bcl-2 was dubious. p53 immunoreactivity did not appear to be predictive of radioresistance in PCa. Cellular response in biopsies shortly after castration therapy might be treatment-predictive.
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PMID:Prognostic factors in prostate cancer. 924 5

The present study evaluated three human prostate xenograft tumors (CWR22, CWR22R, and CWR91) as models for drug activity evaluation. The chemosensitivity and the expression of several proteins (i.e., p-glycoprotein or Pgp, prostate specific antigen or PSA, p53, and Bcl-2) in xenograft tumors were compared with those in patient tumors obtained through radical prostatectomy (n = 26). CWR22 is androgen-dependent, CWR22R is the androgen-independent subline of CWR22, and CWR91 is a separately derived androgen-independent tumor. The results of immunohistochemical and/or Western blot analysis indicate that the expression of PSA, Pgp, p53, and Bcl-2 in the three CWR xenograft tumors are representative of their expression in 100, 85, 90, and 60%, respectively, of patient tumors. The responses of histocultures of xenograft tumors to doxorubicin and paclitaxel, including inhibition of DNA precursor incorporation and cell death induction, were qualitatively similar to the responses of patient tumors. For example, in all three xenograft and patient tumors, doxorubicin produced complete antiproliferation and cytotoxicity (ie., cell kill) whereas paclitaxel produced incomplete effects. A comparison of the concentration-effect relationships in xenograft and patient tumors (population median values) indicates that the chemosensitivity observed in patient tumors is represented by the chemosensitivity of one or more of the three xenograft tumors, as follows: (a) the three xenograft tumors and patient tumors responded equally to doxorubicin-induced antiproliferation; (b) CWR22R, CWR91 and patient tumors responded equally to doxorubicin-induced cytotoxicity, whereas CWR22 was 2-3-fold less sensitive; (c) CWR22 and CWR22R tumors were less sensitive to paclitaxel-induced antiproliferation compared with patient tumors, whereas CWR91 was several-fold more sensitive; and (d) CWR22, CWR22R and patient tumors responded equally to paclitaxel-induced cytotoxicity, whereas CWR91 was 2-3-fold more sensitive. The results of this study indicate that the three xenograft tumors, which show chemosensitivity comparable with the results of > or =50% patient tumors and encompass the majority of the heterogeneous patient prostate tumors in the expression of Pgp, PSA, p53 and Bcl-2 proteins, are useful models for drug activity evaluation.
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PMID:Androgen-dependent and -independent human prostate xenograft tumors as models for drug activity evaluation. 966 91

Molecular studies of bladder carcinomas have aided in determining causative genetic events and the prognosis of cancers endowed with certain abnormalities. In vitro bladder cancer characterization of key cytogenetic alterations is useful for study of molecular changes that may promote oncogenic events. In our laboratory, a novel human bladder cancer cell line, BK10, has been established in vitro and passaged for more than 20 mo. This new bladder cancer cell line (BK10) was derived from bladder tissue containing grade III-IV/IV transitional cell carcinoma. Bladder cancer tissue was obtained at the time of radical cystoprostatectomy extirpation. Cell cultures derived from this surgical sample exhibited an epithelial morphology and expressed epithelial cytokeratins. Immunostains of BK10 were negative for prostate specific antigen (PSA), fibronectin, smooth muscle actin alpha, and desmin. Karyotypic analysis revealed an aneuploid chromosomal content <4n> with many numerical and structural abnormalities previously linked to bladder oncogenesis. Translocations occurred in chromosomes 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 13, 14, 15, 16, 17, 19, 20, 21, 22, X and Y. G-banding analysis revealed rearrangements involving chromosomes 9q and 17p, and the location of the ab11 oncogene and the p53 gene, respectively. The availability of this bladder cancer cell line will provide a useful tool for the further study of bladder carcinoma oncogenesis and gene therapy.
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PMID:Isolation and characterization of a novel human bladder cancer cell line: BK10. 971 13


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