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

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

The expression of oncoprotein, tumor suppressor gene, cellular proliferation and differentiation markers were studied in 64 malignant and benign pancreatic tumors, adjacent and distant to the tumor duct epithelium. Activity of these markers was compared to 16 cases of chronic pancreatitis. Tumor suppressor gene p53 and transforming growth factor alpha were overexpressed in the majority of malignant tumors. The expression of c-erbB-2 oncoprotein and cellular proliferation marker Ki67 was less common in malignant lesions, but was absent in the benign cases. The positive staining of all markers in ductal epithelium outside of the tumor, particularly in pancreatic duct carcinoma, suggest the ductal histogenesis of this malignancy. The presence of c-erbB-2 and Ki67 in malignant lesions only suggest their possible use in the differentiation of pancreatic malignancies and chronic pancreatitis.
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PMID:Expression of p53 tumor suppressor gene, oncoprotein c-erbB-2, cellular proliferation and differentiation in malignant and benign pancreatic lesions. 784 27

New strategies are needed for the detection and treatment of lung cancer and must derive from a fuller understanding of lung carcinogenesis. Frequent molecular genetic abnormalities occur in non-small cell lung cancer (NSCLC), but little is known about which of these precede an invasive carcinoma. We examined the expression of p53, epidermal growth factor receptor (EGFR), and transforming growth factor alpha, the most common molecular genetic abnormalities in NSCLC, in preneoplastic bronchial lesions. Primary NSCLC and associated bronchial lesions were identified by retrospective review of resected tumors at this center. Expression in the invasive carcinomas, the associated bronchial lesions, and normal lung were contrasted using immunohistochemistry. Thirty-four NSCLC associated with 62 bronchial lesions were identified. The invasive tumors included 15 squamous cell carcinomas (SCCs) and 19 non-SCCs. Bronchial lesions included areas of squamous metaplasia (n = 14), inflammatory atypia (n = 19), dysplasia (n = 17), and carcinoma in situ (n = 12). Nineteen (56%) NSCLC and 10 (16%) bronchial lesions exhibited aberrant p53 immunostaining, whereas 18 (53%) NSCLC and 30 (48%) bronchial lesions showed abnormal EGFR immunostaining. Positive staining for transforming growth factor alpha was seen in 16 (47%) NSCLC but occurred inconsistently in the bronchial lesions and in normal bronchial epithelium. Only bronchial lesions associated with squamous cell carcinomas exhibited staining for p53. Aberrant EGFR expression was not associated with a specific type of invasive carcinoma or with specific preneoplastic lesions, although there was a trend toward increased expression in dysplasia and carcinoma in situ relative to metaplasia and atypia. All but one of the NSCLC simultaneously showing aberrant p53 and EGFR staining were SCC. We conclude that: (a) transforming growth factor alpha is variably expressed in normal respiratory epithelium as well as reactive and preneoplastic bronchial lesions; (b) p53 expression is seen in preneoplastic bronchial lesions but is not present in reactive or metaplastic epithelium; (c) aberrant EGFR expression occurs in both reactive and preinvasive bronchial lesions and may be an early marker of neoplastic transformation; and (d) the simultaneous aberrant expression of EGFR and p53 occurs predominantly in SCC and their associated bronchial lesions. These findings indicate that aberrant expression of p53 or the EGFR is frequent in bronchial neoplasia, and coexpression may predispose to the development of squamous cell carcinomas of the lung.
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PMID:Aberrant expression of p53 or the epidermal growth factor receptor is frequent in early bronchial neoplasia and coexpression precedes squamous cell carcinoma development. 788 37

Abnormal expression of p53, transforming growth factor alpha (TGF alpha), epidermal growth factor receptor (EGFR), and c-erbB-2 occurs in a variety of cancers and in some cases is associated with poor prognosis. Immunoperoxidase staining using these markers in formalin-fixed, paraffin-embedded endometrial carcinoma tissue was performed to determine whether immunoreactivity correlates with survival and known prognostic variables. Cases included 84 endometrioid adenocarcinomas, five adenoacanthomas, 12 adenosquamous carcinomas, 11 serous carcinomas, 15 clear cell carcinomas, and one carcinosarcoma for a total of 128 cases. Frequencies of immunoreactivity were as follows: p53, 37 of 128 (29%); TGF alpha, strong (2+) 23 of 128 (18%) and intermediate (1+) 26 of 128 (20%); EGFR, strong (3+) 21 of 128 (16%) and intermediate (2+ or 1+) 83 of 128 (65%); and c-erbB-2, strong (2+) four of 128 (2%) and intermediate (1+) three of 128 (1%). p53 and TGF alpha staining showed statistically significant correlations with decreased length of survival (P < .0017 and P < .0013, respectively, generalized Savage [Mantel Cox]). p53 immunoreactivity correlated with tumor types, grade, and stage. Transforming growth factor alpha staining correlated with increased depth of invasion and presence of vascular invasion. Epidermal growth factor receptor staining did not correlate with length of survival or known prognostic variables. c-erbB-2 staining correlated with tumor type. In the multivariate analysis p53 and TGF alpha staining were not independent predictors of survival when other variables were taken into account, including grade, stage, tumor type, presence of vascular invasion, and depth of invasion. Grade and stage were the only independent predictors of survival when used in combination in a Cox proportional hazards model.
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PMID:Expression of p53, transforming growth factor alpha, epidermal growth factor receptor, and c-erbB-2 in endometrial carcinoma and correlation with survival and known predictors of survival. 792 13

A series of changes in the genes that control hepatocyte growth, or interference with the protein products of these genes, appears to have an important role in the etiology of hepatocellular carcinoma (HCC). Mutations of the p53 tumor suppressor gene have been identified in 30-50% of HCC patients in some geographic areas. Abnormalities of the RB tumor suppressor gene have been found in 20-25% of HCCs, including 80-86% of HCCs with p53 mutations. Overexpression of transforming growth factor alpha (TGF-alpha), insulin-like growth factor II (IGF-II), and the oncogenes N-ras, c-myc, and c-fos have been found in high percentages of HCC patients. The cumulative effect of these changes may be more important than the order in which they occur. Some of these changes may explain the mechanism(s) by which the hepatitis B virus participates in the development of HCC.
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PMID:Tumor suppressor genes, growth factor genes, and oncogenes in hepatitis B virus-associated hepatocellular carcinoma. 804 25

The expression of three epidermal growth factor (EGF)-related peptides, transforming growth factor alpha (TGF-alpha), amphiregulin (AR) and cripto-1 (CR-1), was examined by immunocytochemistry (ICC) in 68 primary infiltrating ductal (IDCs) and infiltrating lobular breast carcinomas (ILCs), and in 23 adjacent non-involved human mammary tissue samples. Within the 68 IDC and ILC specimens, 54 (79%) expressed immunoreactive TGF-alpha, 52 (77%) expressed AR and 56 (82%) expressed CR-1. Cytoplasmic staining was observed with all of the antibodies, and this staining could be eliminated by preabsorption of the antibodies with the appropriate peptide immunogen. Cytoplasmic staining with all of the antibodies was confined to the carcinoma cells, since no specific immunoreactivity could be detected in the surrounding stromal or endothelial cells. In addition to cytoplasmic reactivity, the AR antibody also exhibited nuclear staining in a number of the carcinoma specimens. No significant correlations were found between the percentage of carcinoma cells that were positive for TGF-alpha, AR or CR-1 and oestrogen receptor status, axillary lymph node involvement, histological grade, tumour size, proliferative index, loss of heterozygosity on chromosome 17p or overall patient survival. However, a highly significant inverse correlation was observed between the average percentage of carcinoma cells that expressed AR in individual tumours and the presence of a point-mutated p53 gene. Likewise, a significantly higher percentage of tumour cells in the ILC group expressed AR as compared with the average percentage of tumour cells that expressed AR in the IDC group. Of the 23 adjacent, non-involved breast tissue samples, CR-1 could be detected by ICC in only three (13%), while TGF-alpha was found in six (26%) and AR in ten (43%) of the non-involved breast tissues. These data demonstrate that breast carcinomas express multiple EGF-related peptides and show that the differential expression of CR-1 in malignant breast epithelial cells may serve as a potential tumour marker for breast cancer.
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PMID:Expression of transforming growth factor alpha, amphiregulin and cripto-1 in human breast carcinomas. 818 21

Ionizing radiation (XRT) is often used to treat squamous cell carcinoma of the tongue (SCCT) but little is known of its genetic effects on surviving cancer cells. The effect of XRT on p53, epidermal growth factor receptor (EGFR), and transforming growth factor alpha (TGF alpha) tumor marker expression was evaluated using immunohistochemical analysis in 79 patients with SCCT. Sixty-six patients received no radiation, while 13 received XRT before surgery. Radiation did not influence EGFR or p53 expression. TGF alpha expression, however, was significantly decreased in radiated tumors (15% versus 43%, P = 0.04). These data suggest that XRT either decreases the expression of TGF alpha in SCCT (suggesting a genetic alteration in surviving cancer cells), or does not kill cancer cells with decreased TGF alpha expression. In the latter case, diminished TGF alpha expression may serve as a marker of radioresistance.
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PMID:Radiation treatment decreases transforming growth factor alpha expression in squamous carcinoma of the tongue. 818 Sep 57

The expression of growth factors, such as transforming growth factor alpha (TGF alpha), amphiregulin (AR) and CRIPTO, a type-1 tyrosine-kinase growth factor receptor (erbB-2), and a tumor-suppressor gene (p53), that have been implicated in the development and/or the progression of breast cancer, was evaluated by immunohistochemistry in 100 human primary infiltrating breast carcinomas (IBC). AR and CRIPTO immunoreactivity was also assessed in 55 human breast ductal carcinomas in situ (DCIS). Within the 100 IBC, 80, 50, 73, 17, and 34 tumors expressed moderate to high levels of TGF alpha, AR, CRIPTO, erbB-2, and p53 respectively. In addition, AR and CRIPTO immunoreactivity were found in 11 and in 26 out of 55 DCIS respectively. In contrast, only 4, 3, and 2 out of 10 normal mammary-gland samples were weakly positive for TGF alpha, AR, and CRIPTO expression, respectively, whereas none was positive for erbB-2 or p53. Within the 100 IBC, expression of erbB-2 significantly correlated with high histologic and nuclear grading, with high growth fraction, and with estrogen-receptor (ER)- and progesterone-receptor (PgR)-negative tumors. A statistically significant correlation was also observed between p53 expression and high histologic grading, high growth fraction, and PgR-negative tumors. In contrast, no significant correlations were found between TGF alpha, AR, and CRIPTO immunoreactivity and various clinicopathological parameters, with the exception of a positive correlation between TGF alpha and ER expression. These data demonstrate that TGF alpha, AR, and CRIPTO expression are significantly increased in malignant mammary epithelium relative to normal epithelium. In particular, the differential expression of CRIPTO may serve as a potential tumor marker for breast carcinogenesis.
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PMID:Differential immunohistochemical detection of transforming growth factor alpha, amphiregulin and CRIPTO in human normal and malignant breast tissues. 854 95

Proto-oncogenes, growth factors/receptors, and tumour suppressor genes were analysed in malignant metastatic insulinomas. Normal pancreas showed only a moderate immunoreaction for c-myc proto-oncogene and a strong reaction for insulin. Benign insulinomas were slightly or moderately positive for transforming growth factor alpha (TGF alpha), weakly positive for epidermal growth factor receptor (EGF-R), and strongly positive for c-myc and insulin. In malignant insulinomas, besides a strong immunoreaction for c-myc and TGF alpha, activation of c-K-ras and overexpression of p53 protein were found. Insulin reaction was moderate or strong. Three out of six malignant insulinomas displayed a c-K-ras point mutation at codon 12. All mutations were guanine to cytosine transversion, resulting in amino acid substitution, glycine to arginine. Mutations were present in metastatic insulinomas only. Patients with mutated c-K-ras oncogene had overexpression of p53 protein as well as c-myc and TGF alpha overexpression. Our results support the view that malignant progression is a consequence of more than one genetic lesion and suggest that activation of myc, TGF alpha an ras genes plays a role in a multistep process of tumour progression, perhaps serving as an initiating event.
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PMID:Multiple genetic alterations in malignant metastatic insulinomas. 856 94

The study of 226 cases of hepatocellular carcinoma (HCC) in a homogenous rural Southern African population is based on the assessment of histology, HBV infection, p53 oncoprotein and transforming growth factor alpha (TGFa) expression. Epidemiological and morphological observations were compared to HCC observed in 89 cases from pathological files in Poland and published information from Japan and Italy. Comparatively high number of young patients with HCC in Africa presented high rates of HBV infection, p53 oncoprotein overexpression and high HBsAg/p53 correlation rates. In all patients histological grading of HCC was inversely related to p53 and TGFa expression. No significant differences in histological grading of HCC and patients' mean age were noted between various population groups. The association of hepatic cirrhosis was at least twice as common in non-African patients, whereas iron overload was noted almost exclusively in African patients livers. Signs of HBV infection were lowest in Japanese female patients. The mechanism by which early HBV infection contributes to hepatocarcinogenesis at an early stage of life is confirmed by epidemiological observations in Poland and by the clear association of p53 gene with HBsAg and the age of patients.
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PMID:Hepatocellular carcinoma in young patients: histology, cellular differentiation, HBV infection and oncoprotein p53. 866 53


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