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)

Because of a lack of information of the optimum nutritional requirements, epithelial cells derived from normal human prostate and prostate tumors have been difficult to propagate in vitro, which hinders research in prostate carcinogenesis. In an effort to establish optimum nutritional conditions and differences in growth characteristics of normal human prostate (NP), benign prostatic hyperplasia (BPH), and prostatic carcinoma (PCA), we have compared the effects of several growth factors on cell proliferation and elucidated growth properties of low passage epithelial cells derived from NP, BPH, and PCA of an African-American patient. Primary and low passage cultures were propagated in serum-free keratinocyte basal medium (KBM) supplemented with insulin (5 micrograms/ml), hydrocortisone (0.5 microgram/ml), epidermal growth factor (EGF, 10 ng/ml), bovine pituitary extract (BPE; 50 micrograms/ml), cholera toxin (10 ng/ml), and antibiotics. Almost all NP, BPH, and PCA cells were positive for cytokeratins and prostate-specific antigen (PSA). The NP, BPH, and PCA cells were essentially diploid and lacked mutations in c-K-ras and c-Ha-ras oncogenes, and p53 tumor suppressor gene. However, they exhibited progressively accelerating growth parameters. The population doubling times of NP, BPH and PCA were 51 hr, 37 hr, and 29 hr, respectively; their saturation densities were 2.9 x 10(4)/cm2, 3.3 x 10(4)/cm2, and 7.2 x 10(4)/cm2, respectively. The NP and BPH cells required all of the growth factors in the medium, as deletion of any one of the above factors strongly inhibited their growth. The PCA cells, however, were independent of EGF and hydrocortisone. PC-3, an established human prostate cancer cell line, was independent of the growth factors tested. Fetal bovine serum (FBS) inhibited the growth of NP, BPH and PCA cells. In contrast, FBS stimulated the growth of the PC-3 cells in a concentration-dependent manner. These results indicate that in the absence of any apparent karyotype alterations and mutations in c-K-ras, c-Ha-ras and p53 genes, epithelial cells derived from NP, BPH, and PCA exhibit significant differences in their growth properties and responses to growth factors. These variations may represent early changes involved in prostate cancer, while gene mutations and cytogenetic alterations occur in advanced and/or metastatic tumors.
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PMID:Differential growth factor responses of epithelial cell cultures derived from normal human prostate, benign prostatic hyperplasia, and primary prostate carcinoma. 890 94

Rat liver epithelial cells (RLE) are suspected to be pluripotent hepatic stem cells that give rise to a diverse variety of liver tumors. The molecular events responsible for transformation of these cells and the diversity of the tumor phenotypes remains to be fully elucidated. We examined the genotype and phenotype of RLE cells infected with retroviral shuttle vectors carrying a neomycin resistance (neor) Ha-ras or a lacZ gene. WBneoIII, WBrasIII and WBlacZ cell lines were examined for evidence of a transformed phenotype by comparing their behavior with the parental strain (WB-344) and with WBneo-C-II and WBrasII cells. Confluent cultures of WBneo-C-II and WBrasII cells were found to contain significantly higher numbers of total cells than the other cell lines. The growth rate of WBneo-C-II and WBrasII cells were faster than that of the parental cell line. Addition of epidermal growth factor (EGF) to the medium was found to stimulate the growth rate of WBneo-C-II cells and to induce anchorage independent growth (AIG). No cell line produced tumors in nude mice (nu/nu) except WBrasII cells. Radioimmunoprecipitation studies and sequencing of the p53 exons 5-8 indicate WBneo-C-II, and WBrasII cells produce a mutant p53. Northern blot analysis showed an increased expression of c-myc mRNA in WBneo-C-II and WBrasII cells. These results demonstrate that alterations in critical growth and differentiation controlling genes have occurred in WBrasII cells which may, independent of or in conjunction with ras insertion, cause the transformed phenotype.
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PMID:Phenotypic and genotypic analysis of rat liver epithelial cells infected with retroviral shuttle vectors. 891 62

The incidence of renal cell carcinoma (RCC) has gradually increased, and approximately 40% of all patients diagnosed with this disease will die of it. With the increasing availability of ultrasonography and computed tomography (CT) scanning, incidental renal tumors are more frequently diagnosed. Overall, conflicting evidence still exists to support a trend towards early diagnosis and/or a change in the natural history of the disease. The localization of the von Hippel-Lindau (VHL) tumor suppressor gene and other regions on chromosome 3p have contributed significantly to our understanding of the molecular genetics of both familial and sporadic RCC. Moreover, distinction between different cell types of RCC are being made at the molecular and genetic level. A relationship between environmental factors, such as cigarette smoking, and these genetic disturbances has yet to be determined. Although different determinants of nuclear grading are being proposed as prognostic factors, no convincing evidence has been identified to support the use of other molecular markers, such as the p53 tumor suppressor gene and epidermal growth factor. With regard to treatment, beyond the role of surgery in organ-confined RCC, other therapies for RCC are limited. Furthermore, immunotherapy has shown the best promise by providing durable responses in patients with advanced disease.
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PMID:Renal cell carcinoma: basic biology and clinical behavior. 894 19

Immunoreactivity of bcl-2, p53, the epidermal growth factor (EGFr) and Ki-67 (MIB-1) proteins was assessed by immunohistochemistry in 185 patients with superficial bladder cancer (SBC) in order to evaluate their usefulness as indicators of tumor progression. Forty-one percent of the tumors were bcl-2 positive, 36% of them were positive for p53 (over 20% of nuclei), while 41% were positive for EGFr, and 30% of the tumors were MIB-1 positive (proliferation index > 15%). Immunoreactivity of all analyzed proteins was highly significantly related to tumor grade and stage. Tumors which were bcl-2, p53 or EGFr positive were also rapidly proliferative (MIB-1 score >15%). The obtained results suggest that all analyzed proteins may have prognostic significance in SBC. The prognostic value of the abnormal immunolabeling of the analyzed proteins will be established after an adequate follow-up period of this same cohort of patients.
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PMID:Immunoreactivity of bcl-2, p53 and EGFr is associated with tumor stage, grade and cell proliferation in superficial bladder cancer. Finnbladder III Group. 907 39

In this study we sought factors that determine the survival of human colonic epithelial cells. Normal colonic epithelial cells are dependent on cell-cell contacts and survival factors for the inhibition of apoptosis whereas, during colorectal tumorigenesis, cells develop mechanisms to evade these controls. The ability to survive loss of cell-cell contacts and/or growth factor deprivation is a marker of tumour progression. Many adenoma (premaligant) cultures survive only if cell-cell contacts are maintained in vitro and die by apoptosis if trypsinized to single cells. This also occurs in adenomas derived from familial adenomatous polyposis (FAP) patients, therefore APC mutations do not confer resistance to cell death in response to loss of cell-cell contacts. We show here that if cell-cell contacts are maintained such cells are capable of survival in suspension. Adenoma cells also undergo apoptosis in response to removal of serum and growth factors from the medium. After removal of serum and growth factors c-myc is down-regulated within 2 h. Therefore, the induction of apoptosis is not an inappropriate response of the cells due to a deregulated c-myc gene. The apoptotic response is also p53 independent. Such cultures have been used to determine specific survival factors for colonic epithelial cells. Insulin, the insulin-like growth factors I and II, hydrocortisone and epidermal growth factor (EGF) protect cells from the induction of apoptosis in the absence of serum over a short-term period of 24 h. This approach may give insight into the factors governing growth and survival of colonic epithelial cells in vivo. This is the first report of specific growth factors protecting against apoptosis in human colonic epithelial cells.
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PMID:Cell-cell contact and specific cytokines inhibit apoptosis of colonic epithelial cells: growth factors protect against c-myc-independent apoptosis. 908 30

Apoptosis has become a basic tool in developing cancer research and establishing new cancer strategies. However, the molecular mechanism of apoptosis is not well understood. Recently, the authors found that epidermal growth factor (EGF) induces apoptosis in various cancer cells and that there is a novel signal pathway mediated through p53 in signal transduction of EGF. The effect of antisense gene therapy to p53 tumor suppressor on EGF-dependent apoptosis was investigated in cultured NCI-H 596 human non-small cell lung cancer cells with a wild-type p53 gene. Results showed that EGF plus p53 sense oligonucleotides induced EGF-dependent and p53-dependent apoptosis in NCI-H 596 cells within 8 hours. On the other hand, antisense gene therapy using antisense oligonucleotides to p53 tumor suppressor suppressed the induction of EGF-dependent and p53-dependent apoptosis. Mutated p53 antisense-containing mutated CG dinucleotides had the same effect as that of p53 antisense on suppression of apoptosis in NCI-H 596 cells. We found that a new nucleic acid drug, another mutated p53 antisense-containing mutation at three bases immediately 5' and 3' from the CG dinucleotides, potentiated the induction of apoptosis and failed to suppress the induction of EGF-dependent apoptosis. These results suggest that gene therapy using antisense oligonucleotides to the p53 tumor suppressor is effective on EGF-dependent apoptosis of NCI-H 596 human non-small cell lung cancer.
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PMID:Antisense oligonucleotides to p53 tumor suppressor suppress the induction of apoptosis by epidermal growth factor in NCI-H 596 human lung cancer cells. 914 46

As the molecular events responsible for astrocytoma formation and progression are being clarified, it is becoming possible to correlate these alterations with the specific histopathological and biological features of astrocytoma, anaplastic astrocytoma and glioblastoma multiforme. In WHO grade II astrocytomas, autocrine stimulation by the plateletderived growth factor system coupled with inactivation of the p53 gene may lead to a growth stimulus in the face of decreased cell death with slow net growth ensuing. Such cells would also have defective responses to DNA damage and impaired DNA repair, setting the stage for future malignant change. Such biological scenarios recapitulate many of the clinicopathological features of WHO grade II astrocytomas. Anaplastic astrocytomas further display release of a critical cell cycle brake that involves the CDKN2/p16, RB and CDK4 genes. This results in mitoses seen histologically; clinically, there is more conspicuous, rapid growth. Finally, glioblastomas may emerge from the microenvironmental outgrowth of more malignant clones in a complex vicious cycle that involves necrosis, hypoxia, growth factor release, angiogenesis and clonal selection; growth signals mediated by activation of epidermal growth factor receptors may precipitate glioblastomas. It is clear as well that glioblastoma multiforme can arise via a number of independent genetic pathways, although the clinical significance of these distinctions remains unclear.
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PMID:A molecular genetic model of astrocytoma histopathology. 916 27

We have established an ovarian cancer cell line (CABA I) from ascitic fluid obtained from a patient with papillary adenocarcinoma of the ovary prior to drug treatment. The epithelial origin of the cell line was confirmed by morphology and by immunofluorescence analysis using anticytokeratin antibodies. Ultrastructural analysis revealed a very irregular membrane surface and a clear cytoplasm rich in electron-lucent vesicles. CABA I cells grow rapidly in culture (doubling time 18 h) in an anchorage-independent manner. Exogenously added beta-estradiol and epidermal growth factor (EGF) treatments did not influence cell growth rate. FACS analysis to determine the phenotypic profile of tumor-associated antigen, membrane receptor, and adhesion molecule expression indicated that the cell line was positive for different members of the c-erbB family, for alpha 6 and beta 1 integrin receptors, and intensively positive for HLA class I antigens and the folate receptor. Molecular characterization revealed no mutations for c-myc and c-k-ras genes, but did detect an exon 5 mutation in the p53 gene. CABA I cells grew poorly as heterotransplants in nude mice, and tumors showed long latency periods. Because early (15-20) and late (55-60) passage cells maintain the same growth and phenotypic characteristics, the CABA I cell line might provide a good in vitro model system to investigate the cellular and molecular events involved in ovarian carcinogenesis.
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PMID:Ultrastructural and phenotypic characterization of CABA I, a new human ovarian cancer cell line. 922 Apr 98

Solar UV irradiation is the causal factor for the increasing incidence of human skin carcinomas. The activation of the transcription factor activator protein-1 (AP-1) has been shown to be responsible for the tumor promoter action of UV light in mammalian cells. We demonstrate that proteinase inhibitor I (Inh I) and II (Inh II) from potato tubers, when applied to mouse epidermal JB6 cells, block UV-induced AP-1 activation. The inhibition appears to be specific for UV-induced signal transduction for AP-1 activation, because these inhibitors did not block UV-induced p53 activation nor did they exhibit any significant influence on epidermal growth factor-induced AP-1 transactivation. Furthermore, the inhibition of UV-induced AP-1 activity occurs through a pathway that is independent of extracellular signal-regulated kinases and c-Jun N-terminal kinases as well as P38 kinases. Considering the important role of AP-1 in tumor promotion, it is possible that blocking UV-induced AP-1 activity by Inh I or Inh II may be functionally linked to irradiation-induced cell transformation.
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PMID:Proteinase inhibitors I and II from potatoes specifically block UV-induced activator protein-1 activation through a pathway that is independent of extracellular signal-regulated kinases, c-Jun N-terminal kinases, and P38 kinase. 934 44

We assessed distributions of breast cancer prognostic biomarkers by race/ethnicity and socioeconomic position among paraffin-embedded tumor biopsy specimens from 135 US women (48 white women, 44 black women, 43 Asian women) diagnosed with breast cancer between 1966 and 1990. No racial/ethnic or socioeconomic differences in distributions were observed for tumor stage, lymph node involvement, estrogen, progesterone, and epidermal growth factor receptors, oncogenes such as Her2/neu and p53, cytoplasmic proteins cathepsin-D and ps2, and two indices of cell growth, Ki67 and DNA ploidy, adjusting for age at diagnosis, menopausal status, place of birth and, for racial/ethnic comparisons, working class composition of census block-group at diagnosis. Black and Asian women, however, were 3.5 times (95% confidence interval [CI] = 1.2, 10.1) and 3.7 times (95% CI = 1.3, 10.6), respectively more likely than white women to have a tumor size of > or = 20 mm, and Asian women were 3.4 times (95% CI = 1.1, 10.4) more likely than black women to be positive for androgen receptor, adjusting for these same factors. No differences in distributions by socioeconomic position were observed for these latter two tumor characteristics. These data suggest that racial/ethnic and socioeconomic disparities in breast cancer survival are unlikely to be explained solely by differential distributions of molecular breast cancer prognostic biomarkers.
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PMID:Race/ethnicity, social class, and prevalence of breast cancer prognostic biomarkers: a study of white, black, and Asian women in the San Francisco bay area. 938 54


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