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)

To examine the suggested biological difference between Japanese and British gastric cancers, immunohistochemistry was used to demonstrate eight markers of biological activity in a matched series of 40 Japanese and 33 British cases. There were no differences in the proportions of Japanese and British tumours positive to epidermal growth factor, epidermal growth factor receptor, transforming growth factor alpha, cripto or p53. A significantly greater proportion of British tumours were positive to c-erbB-2 whilst a significantly greater proportion of Japanese tumours were positive to nm23. British tumours had a significantly greater mean proliferating cell nuclear antigen proliferation index than Japanese tumours. These differences could be clinically significant.
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PMID:Are Japanese and European gastric cancer the same biological entity? An immunohistochemical study. 754 52

The limited replicative lifespan of diploid human cells in vitro (cellular senescence) serves as a cellular model of aging. We examined the proliferative response of 2BS cells of different population doubling levels to fibroblast growth factor (FGF). DNA synthesis was measured by thymidine incorporation. As the cells aged, there was a significant decrease in the stimulation of DNA synthesis by FGF addition (P < 0.01). The effective concentration of FGF and the latent period prior to DNA synthesis did not change. Expression of Rb and p53 mRNA after growth factor stimulation was also examined. Young and old cells had similar Rb mRNA levels, whereas the p53 mRNA level was significantly reduced in old cells. After both cells were treated by FGF or epidermal growth factor (EGF), Rb expression increased 210-275% in young cells and 50-60% in old ones. However, no significant change was found in p53 gene transcriptions after FGF addition. The results further suggest that cell aging is associated with a progressive loss of the ability of cells to respond to growth factors.
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PMID:The proliferative response and anti-oncogene expression in old 2BS cells after growth factor stimulation. 756 58

We have characterized 24 hypopharyngeal squamous cell carcinomas and 5 normal hypopharyngeal tissues by immunostaining with antibodies against epidermal growth factor (EGF), EGF-Receptor (EGFR), p53, v-erb B, and ras p21. The Avidin-Biotin Complex (ABC) technique was employed. Overexpression of p53 appeared in 17 of 24 cases of squamous cell carcinoma of the hypopharynx (normal mucosa: none, well differentiated: 60%, moderately differentiated: 71.4%, poorly differentiated: 71.4%). Some dysplastic mucosae surrounding cancer lesions showed overexpression of p53. EGF and EGFR tended to be expressed more strongly in carcinoma [EGF: 29.1% (well differentiated: 30%, moderately differentiated: 28.6%, poorly differentiated: 28.6%); EGFR: 50% (well differentiated: 60%, moderately differentiated: 42.9%, poorly differentiated: 42.9%)] than in normal mucosa (EGF: 0%, EGFR: 20%). The v-erb B stained positively in carcinoma [62.5% (well differentiated: 70%, moderately differentiated: 71.4%, poorly differentiated: 42.9%)] but negatively in normal mucosa. These data suggest that genetic mutations of p53 probably play an important role at an early stage of tumorigenesis, and that the networks of EGF, EGFR and v-erb B probably are involved in the development of hypopharyngeal squamous cell carcinoma.
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PMID:Immunohistochemical study of p53, EGF, EGF-receptor, v-erb B and ras p21 in squamous cell carcinoma of hypopharynx. 761 33

p21WAF1/CIP1 is a nucleoprotein that was initially characterized by its ability to be regulated transcriptionally by p53 and by its ability to mediate growth arrest by binding to cyclin-dependent kinases. Although p21WAF1/CIP1 is thought to mediate the effects of p53 in causing growth arrest, p21WAF1/CIP1 is also regulated in a p53-independent manner, e.g., during terminal differentiation of some cell lines. Growth factors including epidermal growth factor also induce p21WAF1/CIP1 through p53-independent pathways. Because the epidermal growth factor signaling pathway is abnormal in psoriatic epidermis, we studied p21WAF1/CIP1 expression, using in situ hybridization and immunohistochemistry, in psoriasis. Both p21WAF1/CIP1 mRNA and protein were significantly elevated in untreated psoriatic plaques compared with uninvolved psoriatic skin (p < 0.0001), with the up-regulation of p21WAF1/CIP1 being predominantly suprabasal. This increase was accompanied by a small increase in p53 protein expression of uncertain significance. Furthermore, p21WAF1/CIP1 expression was induced in skin after sellotape stripping and by the application of agents, such as dithranol, that are capable of inducing hyperproliferation. The pattern of p21WAF1/CIP1 expression observed is consistent with a role in induction and maintenance of differentiation. Our experiments, however, cannot determine whether the abnormalities of p21WAF1/CIP1 epidermal expression in psoriasis and after insult are independent of changes in p53 expression.
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PMID:Up-regulation of p21WAF1/CIP1 in psoriasis and after the application of irritants and tape stripping. 763 13

Although renal hypertrophy is often associated with the progressive loss of renal function, the mechanism of hypertrophy is poorly understood. In both primary cultures of rabbit proximal tubules and NRK-52E cells (a renal epithelial cell line), transforming growth factor beta 1 (TGF beta) converted epidermal growth factor (EGF)-induced hyperplasia into hypertrophy. TGF beta did not affect EGF-induced increases in c-fos mRNA abundance or cyclin E protein abundance, but inhibited EGF-induced entry into S, G2, and M phases. EGF alone increased the amount of hyperphosphorylated (inactive) pRB; TGF beta blocked EGF-induced pRB phosphorylation, maintaining pRB in the active form. To determine the importance of active pRB in TGF beta-induced hypertrophy, NRK-52E cells were infected with SV40 large T antigen (which inactivates pRB and related proteins and p53), HPV16 E6 (which degrades p53), HPV16 E7 (which binds and inactivates pRB and related proteins), or both HPV16 E6 and E7. In SV40 large T antigen expressing clones, the magnitude of EGF + TGF beta-induced hypertrophy was inhibited and was inversely related to the magnitude of SV40 large T antigen expression. In the HPV16-infected cells, EGF + TGF beta-induced hypertrophy was inhibited in E7- and E6E7-expressing, but not E6-expressing cells. These results suggest a requirement for active pRB in the development of EGF + TGF beta-induced renal epithelial cell hypertrophy. We suggest a model of renal cell hypertrophy mediated by EGF-induced entry into the cell cycle with TGF beta-induced blockade at G1/S, the latter due to maintained activity of pRB or a related protein.
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PMID:Involvement of pRB family in TGF beta-dependent epithelial cell hypertrophy. 769 89

As clinicopathological features may not be sufficient to predict the progression of thymoma, we have carried out what we believe to be the first immunohistochemical study describing the relationship between the different types of thymoma and the tumour stage, on the one hand, and the expression of epidermal growth factor (EGF), EGF-receptor (EGFR), p53, v-erb B and ras p21, on the other. The positive rates versus histological types and Masaoka's clinical stages in the 47 cases were as follows: p53 (non-invasive thymoma: 41.7%; malignant thymoma category I: 82.4%; malignant thymoma category II: 83.3%), EGF (non-invasive thymoma: 4.2%; malignant thymoma category I: 11.8%; malignant thymoma category II: 33.3%) and EGFR (non-invasive thymoma: 8.3%; malignant thymoma category I: 35.3%; malignant thymoma category II: 66.7%); p53 (stages I and II: 51.7%; stages III and IV: 77.8%), EGF (stages I and II: 3.4%; stages III and IV: 22.2%) and EGFR (stages I and II: 13.8%; stages III and IV: 44.4%). These data suggest that p53 may be implicated in the initial stages of tumorigenesis and that increased expression of EGF and EGFR may play a role in thymoma progression.
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PMID:Thymoma: tumour type related to expression of epidermal growth factor (EGF), EGF-receptor, p53, v-erb B and ras p21. 770 23

Squamous carcinoma of the vulva (SCV) is an uncommon neoplasm of uncertain etiology. There is evidence that there are two subgroups of SCV, one associated with human papilloma virus (HPV) and a second HPV-negative group. The UCI-VULV-1 cell line, obtained from a lymph node metastasis of an SCV, grows with a population doubling time of approximately 60 hr. The saturation density is 10(5) cells/cm2. The cell line does not exhibit anchorage independence and is weakly tumorigenic. The cells range in appearance from an abundant spindle cell to a less common larger, flat cell. All of the cells are immunoreactive for high-molecular-weight keratin, but only the flat cells, which form squamous pearls in vivo, are immunoreactive for low-molecular-weight keratin. The cell line expresses epidermal growth factor (EGF), transforming growth factor-alpha, the EGF receptor, and p53 protein. Polymerase chain reaction revealed no HPV DNA within the cells. Early passage cells exhibited karyotypic heterogeneity with few similarities to previous described SCV karyotypes. The cells display sensitivity to cis-platinum in concentrations toxic to many ovarian and cervical carcinoma lines. UCI-VULV-1 may be helpful for studying the properties of the HPV-negative form of SCV.
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PMID:UCI-VULV-1, a vulvar squamous carcinoma cell line. 772 33

Gene expression of growth factors including epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), epidermal growth factor receptor (EGFR), oncogenes such as c-myc, N-ras, c-erbB2 and tumor suppressor gene P53 were studied in 4 human lung cancer cell lines using Northern blot technique. Among these cell lines were 2 adenocarcinoma cell lines, one large cell carcinoma cell line and one small cell carcinoma cell line. Expression of EGF and TGF alpha mRNAs were found in all 4 cell lines and EFGR mRNA was seen in 3 out of 4 cell lines. Among these cell lines, 2 cell lines with weaker expression of EGF and TGF alpha, expressed c-myc mRNA. Another 2 cell lines had no c-myc but expressed large amounts of EGF and TGF alpha mRNA. No expression of N-ras, c-erbB2 and p53 were found in these cell lines. The results indicate the presence of autocrine loop of growth factors in these cancer cells. The autostimulation of growth factors may be the main cause for the uncontrolled growth of cancer cells. After treating the cancer cells with EGF, anti-EGF and anti-EGFR antibodies, EGF was found to exert a mild stimulating effect on the growth of one cell line, but no effect on the other cell lines. Anti-EGF and anti-EGFR antibodies inhibited the cell growth on all cell lines. These results provided further evidence for the presence of autocrine loop of growth factors in these lung cancer cell lines.
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PMID:[Gene expression of growth factors, growth factor receptor and oncogenes in human lung cancer cell lines]. 778 Nov 11

Primary cortical astrocytes were isolated from normal (+/+), heterozygous (+/-), or homozygous (-/-) p53-knockout mice. The normal astrocytes grew slowly and underwent crisis after limited division, while the homozygously defective cells grew rapidly and without contact inhibition. These -/- cells could not initially form colonies in soft agarose but acquired this capability after 10 passages in FCS or basic fibroblast growth factor but not epidermal growth factor. Almost all -/- astrocytes weakly expressed glial fibrillary acidic protein at passage 10 and were also A2B5+ when cultured in basic fibroblast growth factor. Most heterozygous cells resembled normal ones; however, some survived crisis, grew rapidly, and formed colonies. Outgrowing cells had all lost the wild-type p53 allele. These molecular and cellular events mimic the early stages of human brain tumors, suggest a role for p53 in the earliest stages of disease progression, and provide an experimental system to analyze the effects of other tumor-specific mutations in the disease process.
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PMID:Loss of wild-type p53 bestows a growth advantage on primary cortical astrocytes and facilitates their in vitro transformation. 779 98

Over-expression of transforming growth factor-alpha (TGF-alpha) is consistently seen in spontaneous transformants of rat liver derived epithelial cells (RLE phi 13) and has been implicated in the transformation of other cultured cells. We have constitutively over-expressed TGF-alpha in RLE phi 13 cells, which are known to express epidermal growth factor receptors, to determine if TGF-alpha over-expression plays a role in transformation or differentiation, or both, of these cells. Early passage RLE phi 13 cells were infected with a replication-defective murine retrovirus that expresses both the full length coding sequence for human TGF-alpha and the neomycin-resistance gene. Integration of the transcriptionally active provirus and expression of TGF-alpha mRNA were confirmed. Neither morphologic transformation nor molecular evidence for differentiation was noted in TGF-alpha-producing clones. However, these clones did exhibit an accelerated growth rate, increased expression of several cell cycle related genes including mitotic cyclic B1, proliferating cell nuclear antigen, c-myc, and p53 as well as increased expression of the preneoplastic marker enzyme, glutathione-S-transferase. This suggests that over-expression of TGF-alpha results in increased cell cycling, and that subsequent events must be necessary for cellular transformation or differentiation or both.
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PMID:Constitutive over-expression of transforming growth factor-alpha in rat liver epithelial cells leads to increased cell cycling without transformation. 782 Mar 13


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