Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hormonal manipulation of prostate cancer is an effective therapy for metastatic disease. Unfortunately, following an initial response tumors reestablish themselves as hormone independent variants and progress. This study was designed to assess the interrelationship of cytokeratin P (Cyto P), vimentin, epidermal growth factor receptor (rEGF) and tissue testosterone following androgen deprivation therapy. Animals bearing the hormone dependent Dunning R3327 G subline prostatic adenocarcinoma were surgically castrated and progressing tumors from both hormone intact and castrated groups were quantitatively assayed for immunohistologic reactivity against the described markers. The results demonstrate a significant (p < 0.05) decrease in cytokeratin (Cyto P), rEGF and testosterone levels following castration. When the expression of both rEGF and Cyto P are related to the tissue testosterone content, it is observed that the ratio between rEGF and testosterone remains essentially unchanged (0.65 +/- 0.21 to 0.65 +/- 0.41), suggesting that in the Dunning R3327 G subline, rEGF expression is coordinately under androgen control. At least some cytokeratin expression also appears to be particularly sensitive to androgen levels, since the ratio between Cyto P and testosterone decreased from 0.92 +/- 0.39 to 0.35 +/- 0.41 following castration. In contrast, following castration, the expression of vimentin was unaffected.
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PMID:Coordinate loss of growth regulatory factors following castration of rats carrying the Dunning R3327 G prostatic tumor. 128 86

Expression of the p53, the epidermal growth factor receptor (c-erbB-1) and c-erbB-2 protein was studied in 34 men with benign prostatic hyperplasia and 29 men with locally advanced prostate cancer by means of an immuno-histochemical method. Strong staining for p53 was found in five of 29 prostate cancers (17%; mean 21% +/- 7% of malignant cells stained in the positive tumours), but no staining was found in benign prostatic hyperplasia (p less than 0.05). On the other hand, the epithelium in benign glands was stained positively for c-erbB-2 in 18% (6/34) and for the epidermal growth factor receptor in 88% (30/34); whereas malignant epithelium stained strongly for c-erbB-2 in 21% (6/29) and for the epidermal growth factor receptor in only 17% (5/29). Prostate cancer was associated with a significant decrease in epidermal growth factor receptor staining (p less than 0.0001) and a significant increase in p53 staining (p less than 0.05). Most of the tumours were advanced and no significant relationship was observed between tumour stage and grade and expression of p53, the epidermal growth factor receptor or c-erbB-2. These findings demonstrate that altered expression of the epidermal growth factor receptor and p53 protein occurs in prostate cancer, but were not associated with other features of prognostic importance such as stage or grade.
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PMID:p53, c-erbB-2 and the epidermal growth factor receptor in the benign and malignant prostate. 137 Jul 1

The use of multiple tumor markers could better predict the behavior of malignant tumors. In prostate cancer, there are no reliably predictive markers for metastatic behavior but the histologic grade and clinical stage of tumor do influence prognosis. We have determined the expression of blood group antigens A, B, H, Lewis-a and Lewis-b and the proto-oncogene proteins v-erbB, c-fos and v-H-ras in both benign and malignant prostate tissues by immunohistochemistry. We determined the relationship between these markers and the grade of malignancy and by inference, clinical behavior. There was reduced expression of blood group antigens A, Lewis-a and Lewis-b in all grades of prostatic adenocarcinoma. We also found that the expression of v-erbB was greater in tumors of high grade. We suggest that loss of blood group antigens may be correlated with elevated v-erbB oncoprotein expression (related to epidermal growth factor receptor) and increasing grade of prostatic malignancy.
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PMID:Correlation of blood group antigen expression and oncogene-related proteins in malignant prostatic tissues. 171 71

Androgen-independent prostate cancer cells may rely on an autocrine loop for growth stimulation, and have been shown to express both the epidermal growth factor receptor (EGFR) and its stimulatory ligands. We have shown here that DU 145 prostate cancer cells have a decreased amount of EGFR in confluent cultures when compared to levels seen in subconfluent cultures. This down-regulation of EGFR numbers is not due to cell proliferation or nutrient depletion, but can be correlated only with whether cell-cell contact exists throughout the culture. This is reminiscent of the situation existing in some tumors whereby EGFR expression is higher in cells at the invading margins of the tumor.
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PMID:Density-dependent regulation of epidermal growth factor receptor expression in DU 145 human prostate cancer cells. 187 36

We surveyed the tumor-related proteins present in the urine specimens of 118 bladder cancer patients to seek a possible marker enabling future diagnosis and prognosis of this disease. We identified a protein of 180 kDa. by sodium dodecyl sulfate polyacrylamide gel electrophoresis in urine samples subjected to prior adsorption by protein-A conjugated to a sepharose bead. This protein appears to be a glycoprotein because it binds to concanavalin A-conjugated sepharose and can be eluted by alpha-methyl D-mannoside. It does not react immunochemically with antibodies prepared against either carcinoembryonic antigen or epidermal growth factor receptor, both of which have an apparent molecular weight close to 180 kDa. We found this protein in the urine of 74.3% of the patients with transitional cell carcinoma. It was not present in age-matched controls, patients with benign prostatic hyperplasia or patients with 10 other cancers. There was 1 false positive result in a patient with prostate cancer. It does not appear to be associated with urinary tract infection, blood contamination, premedication or anesthesia.
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PMID:A new 180 kDa. urine protein marker associated with bladder cancer. 235 80

Enhanced expression of the epidermal growth factor receptor (EGFR) or its ligands, epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha) can increase signalling via receptor-mediated pathways which may lead to excessive proliferation and cellular transformation. Such autocrine regulation of growth has been demonstrated for prostate cancer cell lines in culture but its role in prostate cancer in vivo has not been established. To assess the potential of such a mechanism, we have examined the pathway components in prostate carcinomas (CaP) in comparison with non-malignant benign prostatic hyperplasias (BPH). In the present study, we investigate the dosage, structure and expression of EGF, TGF-alpha and EGFR genes in a series of 34 human prostate samples and 3 prostate cancer cell lines. All of the samples contained transcripts from each of the genes. The expression of pre-pro-TGF-alpha mRNA and pre-pro-EGF mRNA were significantly higher in CaP (n = 13) than BPH (n = 21) specimens (p < 0.05). The androgen-responsive prostatic carcinoma cell line, LNCaP, expressed high levels of EGF mRNA while the androgen-independent DU145 and PC-3 cell lines expressed high levels of TGF-alpha mRNA and EGFR mRNA. In general, overexpression of these mRNAs was not associated with amplification or detectable gene rearrangement; only DU145 cells demonstrated any alteration in these genes, with apparent amplification of the TGF-alpha gene. Relative to BPH, all prostate carcinomas and cell lines studied had elevated levels of mRNA for one or both mRNA coding for the ligands for EGFR.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of mRNA for epidermal growth factor, transforming growth factor-alpha and their receptor in human prostate tissue and cell lines. 750 78

In order to more clearly define the status of epidermal growth factor receptor (EGFR) in prostate cancer, expression of EGFR transcript and protein was analyzed in paired samples of benign and malignant tissues from 30 radical prostatectomy specimens. Prostate tumors and high grade prostatic intraepithelial neoplasias (PINs) expressed significantly less EGFR protein than benign tissues or low grade PINs (P < 0.001). Expression of EGFR mRNA was analyzed in a subset of the same samples, and was higher in more prostate tumors than benign specimens (P < 0.05). However, differences in mean mRNA expression between malignant and benign tissues were not significant. EGFR mRNA was expressed at moderate or low levels in equivalent numbers of PIN lesions. These results suggest that, although EGFR mRNA expression is somewhat elevated in prostate tumors, EGFR protein expression may be down-regulated in the same malignant tissues. Furthermore, our data demonstrate phenotypic similarity between prostate tumors and high grade PIN at the level of EGFR protein expression.
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PMID:Comparative analysis of epidermal growth factor receptor gene expression and protein product in benign, premalignant, and malignant prostate tissue. 752 60

The long-term propagation of primary human prostate cancer (PCA) in vivo or in vitro has been rare. Most such PCAs are phenotypically different from most PCAs in humans; i.e., they make little prostate specific antigen and respond little, if at all, to androgen deprivation. A serially transplantable, primary human PCA, designated CWR22, exhibits a clonal cytogenetic aberration, causes high elevations of prostate specific antigen in the peripheral blood of nude mice, and is unusually responsive to androgen deprivation as compared with other xenografts. Studies of mRNA from CWR22 have demonstrated the expression of prostate specific antigen and the epidermal growth factor receptor family including erbB1/epidermal growth factor receptor, erbB2/neu, and erbB3, but not erbB4. A ligand for these receptors, the neu differentiation factor, is also expressed.
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PMID:CWR22: androgen-dependent xenograft model derived from a primary human prostatic carcinoma. 752 52

Cells respond to certain soluble factors that bind to cell surface receptors possessing intrinsic tyrosine kinase activity. Overexpression of these molecules has been associated with tumor progression. Enhanced prostatic cancer cell growth in vitro has been reported in the presence of certain growth factors. To characterize the patterns of expression of the epidermal growth factor receptor (EGFr) and transforming growth factor-alpha (TGF alpha), we studied tissue from 107 prostate specimens using immunohistochemistry. We observed that epithelial cells of normal (n = 4) and benign prostatic (n = 56) tissues express EGFr but were unreactive for TGF alpha, while stroma cells in these tissues express TGF alpha but not EGFr. However, coexpression of EGFr and TGF alpha was identified in 22 of 46 prostatic adenocarcinomas studied. These results suggest that the major mode of action of EGFr/TGF alpha in normal and benign prostate is that of a paracrine or juxtacrine loop, the ligand being expressed in the stroma cells and the receptor in the epithelial cells. Since a subset of prostatic carcinomas coexpressed the ligand and the receptor in their tumor cells, it is suggested that an independent autocrine signaling mechanism may occur and grant a selective advantage for the growth of prostate cancers.
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PMID:Expression of transforming growth factor-alpha and the epidermal growth factor receptor in human prostate tissues. 752 98

Immunohistochemical examination of radical prostatectomy specimens from 57 patients was performed to determine the differential expression of transforming growth factor alpha in the human prostate. In addition, epidermal growth factor receptor (EGFr) immunoreactivity was assessed in each case. Stromal versus epithelial staining was determined for each histological subtype: benign prostatic hypertrophy (BPH), prostatic intra-epithelial neoplasia (PIN), and prostatic cancer (CaP) by a single pathologist reviewer. TGFa staining was predominant in stroma while EGFr was localized to the epithelial basal cell layer. Immunoreactivity of both TGFa (P = 0.002) and EGFr (P < 0.001) revealed a significant reduction in CaP compared to BPH or PIN. Autocrine stimulation of EGFr by TGFa or other unrecognized factors may be present in CaP. Conversely, altered stromal influence of CaP via TGFa may be present. These observations could form the basis for future cancer therapeutic strategies using antagonist factors.
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PMID:Differential immunoreactivity of transforming growth factor alpha in benign, dysplastic and malignant prostatic tissues. 753 May 64


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