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)

A new cell line, CUMC-3, has been derived from an invasive nonkeratinizing squamous cell carcinoma of the uterine cervix in a 32-year-old patient. It has been maintained in long-term culture for 59 months, and passaged over 310 times. Monolayer-cultured cells were polygonal in shape, showing a pavement-like arrangement and a tendency to pile up without contact inhibition. The epithelial nature of the cultured CUMC-3 cells was also confirmed by transmission electron microscopy which demonstrated the presence of desmosomes and tonofilaments. The cells were highly tumorigenic in nude mice and the transplanted tumors were poorly differentiated squamous carcinoma which closely resembled the original tumor. Cultured cells obtained from the CUMC-3-derived nude mouse tumor, CUMC-3N, also were studied for its characterization. Repeated chromosome analysis revealed a stable clone with the modal chromosome number of 78. The metaphase of this cell line had multiple structural aberrations of chromosomes 1, 3, 8, 10, 11, 20, and X and showed several markers of unknown origin. The results of isozyme analyses were distinct from the HeLa cell line. The identical genetic signature was demonstrated both in CUMC-3 and in CUMC-3N cells. Cultured CUMC-3 cells produced human chorionic gonadotropin beta-subunit and tumor antigen of squamous cell carcinoma (TA-4). Cytosol estrogen receptors were found in this cell line but progesterone receptors were not measured. HLA typing of CUMC-3 cells indicated the presence of DR4, DR8, DQw3, and DQw6. The result of oncogene analysis using Southern blotting technique revealed no amplification of oncogene c-myc. Analysis of the DNA samples extracted from the CUMC-3 cells showed the presence of human papillomavirus type 16 DNA. Using the single-strand conformation polymorphism technique, we have screened CUMC-3 cells for p53 mutation in exons 4 to 9. No mobility shift was observed in this cell line. This cell line may be useful in studying the in vitro and in vivo properties of human cervical carcinoma.
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PMID:Establishment and characterization of a cell line (CUMC-3) derived from a human squamous carcinoma of the uterine cervix. 770

A case is presented of pulmonary blastoma occurring in the right upper lobe of a 25-year-old man without distinct clinical features and laboratory abnormality. Light microscopic analysis revealed that the tumor was composed of branching glands and morulae embedded in a primitive but bland mesenchyme. Immunohistochemically the epithelial cells were immunoreactive for cytokeratins, S-100 protein, protein gene product 9.5, chromogranin A, calcitonin, and Ki-67 (MIB-1); the mesenchymal cells were immunoreactive for vimentin, actin, cytokeratins, and Ki-67; and all the tumor cells were negative for p53, estrogen receptor protein, and human chorionic gonadotropin beta. Characteristically, many epithelial cells contained optically clear nuclei which were immunoreactive for biotin (M743). Electron microscopic analysis revealed that the optically clearing change was due to replacement of the central area of the nuclei by a mass of parallel-arranged 7- to 10-nm filaments, and biotin-immunoreactive products were mainly localized in the nuclear matrix. Additionally, spherical bodies were identified in the cytoplasm of the nuclear filament-aggregated cells, suggestive of an intimate pathogenetic association of the two morphological abnormalities. The similarity of the aggregated nuclear filaments to those observed in gestational endometrium and ovarian endometrioid carcinoma implies that a similar mechanism plays a role in the pathogenesis of these abnormalities.
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PMID:Pulmonary blastoma: an ultrastructural and immunohistochemical study with special reference to nuclear filament aggregation. 859 6

Four examples of spermatocytic seminoma with a predominant anaplastic component occurred in men 33 to 43 years of age, without histories of cyptorchidism. The seminomas presented with painless testicular masses recognized 3 to 18 months before orchiectomy. Preoperative serum measurements of human chorionic gonadotropin and alpha-fetoprotein were negative. All tumors contained areas (10% to 30% of the tumor) in which the three cell types characteristic of conventional spermatocytic seminoma could be identified under light microscopy. The predominant anaplastic component also contained the three cell types, but the nuclei had prominent nucleoli with granular and filamentous chromatin. In addition, sheets of cells with vesicular nuclei and prominent nucleoli superficially resembling embryonal carcinoma were found. There were numerous large mononuclear and multinucleated giant cells with bizarre nuclei and prominent nucleoli, but no sarcomatous elements. Many normal and abnormal mitotic figures were present. Tunical and vascular invasion and extensive necrosis were constant features. Immunohistochemistry documented p53 protein overexpression in two tumors, but neoplastic cells were negative with immunostains for placenta-like alkaline phosphatase, leukocyte common antigen, neuron-specific enolase, alpha-fetoprotein, human chorionic gonadotropin, vimentin, and cytokeratins. Ultrastructural examination of the anaplastic component showed large rope-like nucleoli, but the cytoplasmic features were similar to those of conventional spermatocytic seminoma. Despite the presence of a major anaplastic component, no patient has developed metastasis. Larger series and longer follow-up are needed to understand the natural history of these neoplasms.
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PMID:Anaplastic variant of spermatocytic seminoma. 869 7

A new cell line, CUMC-6, has been derived from an invasive nonkeratinizing squamous cell carcinoma of the uterine cervix in a 31-year-old patient. It has been maintained in long-term culture for 61 months, and passaged over 300 times. Monolayer-cultured cells were polygonal in shape, showing a pavement-like arrangement and a tendency to pile up without contact inhibition. The epithelial nature of the cultured CUMC-6 cells was confirmed by transmission electron microscopy which demonstrated the presence of desmosomes and tonofilaments. The subcutaneous injection of cultured cells into nude mice gave rise to fast-growing tumors. The transplanted tumor showed similar histological features, but poor differentiation compared to the original tumor. Cultured CUMC-6 cells produced human chorionic gonadotropin beta-subunit (beta-HCG) and alpha-fetoprotein (AFP). Cytosol estrogen and progesterone receptors were not measured in this cell line. The results of isozyme analyses were distinct from the HeLa cell line. Repeated chromosome analysis from passage 6 to 300 revealed that most metaphases of this cell line contained diploid number of chromosomes. The structural abnormality consistently observed in this cell line was the elongation of short arm of chromosome 1. The G- or R-banded pattern of this chromosome suggested inv dup (1) (1pter-->1p34[symbol: see text] 1p21-->1p34[symbol: see text] 1p34-->1qter). Human leukocyte antigen (HLA) typing of CUMC-6 cells indicated the presence of DR12 and DQw3. Analysis of the DNA extracted from the CUMC-6 cells showed the presence of human papillomavirus (HPV) type 16 and 18 DNAs. The results of oncogene analyses using Southern blotting technique revealed amplification and rearrangement of oncogene c-myc and no amplification of oncogene L-myc. Using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique, we have screened CUMC-6 cells for p53 mutation in exons 4 to 9. No mobility shift was observed in this cell line. These results suggest that chromosome 1 abnormality, oncogene alteration, and HPV infection work together in cervical tumorigenesis.
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PMID:CUMC-6, a new diploid human cell line derived from a squamous carcinoma of the uterine cervix. 875 55

Human chorionic gonadotropin (hCG) inhibits the progression of 7,12-dimethylbenz[a]anthracene (DMBA) induced mammary carcinomas. In order to determine whether this phenomenon was mediated by induction of programmed cell death or apoptosis, 45-day-old virgin Sprague-Dawley rats received 8 mg DMBA/100 g body weight; 20 days later they were injected daily with 100 IU hCG for 40 days (DMBA + hCG group). Age-matched untreated, hCG- and DMBA + saline treated rats were used as controls. Tissues were collected at the time of DMBA administration and at 5, 10, 20 and 40 days of hCG injection. RNA from mammary glands, adenocarcinomas and ovaries was probed for transforming growth factors (TGF) alpha and beta, and the apoptotic genes TRPM2, ICE, bcl2, bcl-XL, bcl-XS, p53 and c-myc. The mammary glands of hCG-treated animals with or without DMBA exhibited elevated expression of TRPM2, ICE, bcl-XS, c-myc and p53; and elevation in the apoptotic index. Mammary adenocarcinomas developed in those animals treated with hCG showed an elevation in the expression of p53, c-myc and ICE genes in comparison with the levels detected in the adenocarcinomas developed by the animals treated with DMBA alone. No significant alterations in the expression of any of the genes tested was observed in ovarian RNAs. These results led us to conclude that hCG induces programmed cell death in the mammary gland initiated in the carcinogenic process, that this process is p53 dependent, and is modulated by c-myc expression. Our data also indicate the possibility that a cell death program dependent on the bcl2 family exists, because of the potential involvement of p53, bcl-XS and Bax in apoptosis. This additional mechanism of tumor inhibition makes hCG treatment a useful approach for the prevention and therapy of breast cancer.
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PMID:Chorionic gonadotropin inhibits rat mammary carcinogenesis through activation of programmed cell death. 932 78

Intermediate trophoblast (IT) rarely gives rise to a placental site trophoblastic tumor (PSTT) To examine the different growth mechanisms present in normal and neoplastic IT, the expression of cell cycle regulatory molecules was compared at normal implantation sites and in PSTTs. Normal implantation sites in early gestation (19 patients) and PSTTs (6 patients) were immunohistochemically studied using antibodies against cytokeratin, human chorionic gonadotropin, and human placental lactogen to identify IT, and antibodies against Ki-67, cyclins (A, B, D1, and E), cyclin-dependent kinases (cdks), and p53 to investigate the proliferative activity of the trophoblast. Marked proliferative activity was observed in the trophoblast of the cell columns. Normal IT exhibited a very low labeling index for Ki-67, with negative expression for cdks and cyclins, except for cyclins B and E. The tumor cells of PSTT exhibited a high labeling index for Ki-67 with positive expression for all the cyclins and cdks examined. Expression of p53 was identified in tumor cells of PSTTs and the distribution of p53-positive cells correlated topographically with that of the cyclin A-positive cells. The transformed IT of PSTT has high proliferative activity with an abnormal expression of cell cycle regulatory molecules, which is not observed in normal IT.
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PMID:Immunohistochemical analysis of cell cycle regulatory gene products in normal trophoblast and placental site trophoblastic tumor. 965 19

The glycoprotein hormone, human chorionic gonadotropin (hCG) inhibits mammary tumorigenesis through induction of differentiation, and inhibits the proliferation of human breast epithelial cells (HBEC) in vitro. The present study was designed to determine whether the inhibitory effects of hCG was associated with the modulation of apoptotic gene expression. MCF-10F, a normal immortalized HBEC, BP1-E, a benzo(a)pyrene (BP) transformed cell line, and the urothelial cell line T24, were treated with 100 IU/ml of a commercially available preparation of hCG. Cell growth analysis and RNA extraction for determination of apoptotic gene expression were performed at 24 and 120 hrs of hCG treatment. Both hCG-treated and control cells grew at similar rates for the first 24 hours. A significant reduction in the number of viable MCF-10F and BP1-E cells occurred by 120 hours of treatment, whereas the number of both hCG treated and control T24 cells were similar. Northern blot analysis revealed that the 24 hour-hCG treatment induced an elevation in the expression of the apoptotic genes TRPM2, ICE, TGF-beta, p53, bax, and p21WAF1/CIP1 in MCF-10F cells. By 120 hours of treatment MCF-10F cells maintained the same level of gene expression observed at 24 hours, except for a reduction in c-myc and bax. Control cells exhibited an elevation in the expression of TRPM2, TGF-beta, p53, bax, and p21WAF1/CIP1, whose levels became similar to those observed in hCG-treated cells. The 24 hour-treated BP1-E cells showed activation of ICE, bax and p21WAF1/CIP1. However, TRPM2 expression was moderately activated. By 120 hours TRPM2, ICE, TGF-beta, c-myc and p21WAF1/CIP1 were elevated in both treated and control cells except bax which was slightly down-regulated. The levels of bc12 were significantly decreased by hCG treatment. Gene expression was not modified by hCG treatment in T24 cells. Our findings suggest that hCG induced an acceleration in the expression of apoptotic genes, which became evident before detection of cell growth inhibition. Gene activation differed among immortalized, and chemically transformed cells, suggesting that hCG might utilize both p53 dependent and p53 independent pathways for inhibiting cell cycle progression. The importance of these findings lies in the potential use of agents like hCG for the chemoprevention and chemotherapy of breast cancer.
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PMID:Growth inhibition and activation of apoptotic gene expression by human chorionic gonadotropin in human breast epithelial cells. 989 38

Breast cancer is more frequent in nulliparous women, while its incidence is significantly reduced by full-term pregnancy. The fact that the protection conferred by pregnancy is observed in women from different countries and ethnic groups, regardless of the endogenous incidence of this malignancy, indicates that this protection does not result from extrinsic factors specific to a particular environmental, genetic, or socioeconomic setting, but rather from an intrinsic effect of parity on the biology of the breast. Using an experimental system we have shown that treatment of young virgin rats with human chorionic gonadotropin (hCG), like full-term pregnancy, efficiently inhibits the initiation and progression of chemically induced mammary carcinomas. Treatment of young virgin rats with hCG induced a profuse lobular development of the mammary gland, reduced the proliferative activity of the mammary epithelium, and induced the synthesis of inhibin, a secreted protein with tumor-suppressor activity. HCG treatment also increased the expression of the programmed cell death (PCD) genes testosterone repressed prostate message 2 (TRPM2), interleukin 1-beta-converting enzyme (ICE), p53, c-myc, and bcl-XS, induced apoptosis, and downregulated cyclins. PCD genes were activated through a p53-dependent process, modulated by c-myc, and with partial dependence on the bcl-2 family-related genes. The possibility that this hormonal treatment activates known or new genes was tested by differential display technique. We have identified a series of new genes, hormone-induced-1 (HI-1) among them. The characterization of their functional role will contribute to clarify the mechanisms through which hCG inhibits the initiation and progression of mammary cancer. Of great significance was the observation that PCD genes remained activated even after lobular formations had regressed due to the cessation of hormone administration. We postulate that this mechanism plays a major role in the long-lasting protection exerted by hCG from chemically induced carcinogenesis, and might be also involved in the lifetime reduction in breast cancer risk induced in women by full-term pregnancy. The implications of these observations are two-fold: on one hand, they indicate that hCG, as pregnancy, may induce early genomic changes that control the progression of the differentiation pathway, and on the other, that these changes are permanently imprinted in the genome, regulating the long-lasting refractoriness to carcinogenesis. The permanence of these changes, in turn, makes them ideal surrogate markers of hCG effect in the evaluation of this hormone as a breast cancer preventive agent.
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PMID:Hormonal approach to breast cancer prevention. 1076 7

Prostanoids influence differentiation in diverse cell types. Altered expression of cyclooxygenase and prostaglandins has been implicated in the pathophysiology of placental dysfunction, which results in preeclampsia and fetal growth restriction. We hypothesized that prostanoids modulate differentiation and apoptosis in cultured human trophoblasts. Villous cytotrophoblasts were isolated from term human placentas and cultured in serum-free medium. The level of human chorionic gonadotropin was used as a marker of biochemical differentiation of primary trophoblasts, and syncytia formation was used as a marker of morphologic differentiation. Of the prostanoids tested, we found exposure to thromboxane A(2) hindered both biochemical and morphologic differentiation of cultured trophoblasts. As expected, human chorionic gonadotropin levels in the media were elevated in a concentration-dependent manner in the presence of the thromboxane synthase inhibitor, sodium furegrelate, or the thromboxane A(2) receptor blocker SQ 29,548. Furthermore, thromboxane A(2) enhanced trophoblast apoptosis, determined using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining, cell morphology, and a concentration-dependent increase in p53 expression. We conclude that thromboxane A(2) hinders differentiation and enhances apoptosis in cultured trophoblasts from term human placenta. We speculate that thromboxane may contribute to placental dysfunction by restricting differentiation and enhancing apoptosis in human trophoblasts.
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PMID:Thromboxane A(2) limits differentiation and enhances apoptosis of cultured human trophoblasts. 1147 4

Granulosa cell luteinization involves the attenuation of gonadotropin-induced proliferation. Although recent evidence indicates that primate granulosa cells stop dividing within 12 h of an ovulatory stimulus, early events in cell cycle arrest remain unknown. In the current study an in vitro model of primate granulosa cell luteinization is established that allows assessment of early events in terminal differentiation. A luteinizing dose of human chorionic gonadotropin (hCG) results in a secondary rise in proliferation before cell cycle arrest that is paralleled by a transient increase in the expression of c-Myc. In contrast, the c-Myc antagonists Mad1, Mad4, and Mxi1 are transiently repressed by hCG. Max, the common dimerization partner for Myc and Mad, is similarly repressed by hCG, suggesting that changes in the expression of this gene may further regulate the activity of Myc and Mad. To determine whether other cell cycle regulatory families are involved in luteinization, the expression of p53 and the wild-type p53-inducible phosphatase (wip1) was examined. Similar to Mad and Max, p53 and wip1 are transiently repressed by hCG, suggesting that the p53 and Mad pathways have either parallel or cooperative roles in luteinization. Thus, luteinization of primate granulosa cells is preceded by a burst of proliferation that is regulated by changes in the relative levels of c-Myc, Max, and Mad as well as p53.
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PMID:Dynamics of Myc/Max/Mad expression during luteinization of primate granulosa cells in vitro: association with periovulatory proliferation. 1263 7


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