Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

From a single spontaneous feline mammary carcinoma, two subpopulations of epithelial tumor cells have been isolated. The variant cells were established as cell lines designated K248C and K248P. DNA ploidy analysis showed that the two cell lines represented cell populations already present in the original tumor. Chromosome analysis confirmed the feline origin of K248C and K248P and demonstrated that in addition to unique marker chromosomes characteristic for each cell line, both cell lines had several marker chromosomes in common. These data suggest that the two cell populations arose from a hypothetical single ancestor which diverged during tumor progression. The K248C and K248P cell lines differed from one another with respect to their tumorigenicity in athymic mice and epidermal growth factor (EGF) receptor content. The K248C cells were highly tumorigenic as indicated by a short latency period and high take rate. The K248P cells were poorly tumorigenic. Southern blot analysis revealed that the K248C cells contained an amplified EGF receptor gene that was accompanied by elevated levels of EGF receptor RNA and protein. The K248C cells were growth inhibited in vitro at EGF concentrations that stimulated growth of K248P cells. The amplification of the EGF receptor gene could be detected only in DNA derived from K248C cells at high passage numbers and not in DNA derived from the original tumor and K248C cells at low passage numbers. These data suggest that amplification of the EGF receptor gene occurred during establishment of the K248C cell line.
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PMID:Isolation of two distinct epithelial cell lines from a single feline mammary carcinoma with different tumorigenic potential in nude mice and expressing different levels of epidermal growth factor receptors. 164 97

Immunohistochemical characteristics of undifferentiated carcinomas of the ovary were examined using formalin-fixed, paraffin-embedded tissues with an avidin-biotin staining approach. Eight cases were collected from the pathology files of our Institute from a total of 214 recorded malignant ovarian tumors. For immunostaining, antibodies reacting with epithelial membrane antigen (EMA), pankeratin, vimentin, CA 125, CA 19-9, carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), alpha-1-antitrypsin (AT), epidermal growth factor receptor (EGFR), c-erbB-2, bcl-2 and p53 proteins were used. All the cases examined were positive for EMA and pankeratin, specific markers for epithelial tumors, negative for the non-epithelial tumor marker, vimentin, and also positive for EGFR. Interestingly, only one case was positive for CA 125, despite it being one of the commonest reported indicators of ovarian cancer. CA 19-9 was positive in 7 cases, CEA in 5, AFP in 2, AT in 6 and c-erbB-2 protein in 4. Two cases were positive for p53 protein, and in 1 of these positive staining for bcl-2 was also observed. These results indicate that the epithelial nature is well preserved in undifferentiated ovarian carcinomas, although consistently positive reactions were not observed within the cases for some antigens. They further clearly show that a negative signal for CA 125 can not be considered to exclude the possibility of a primary ovarian tumor.
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PMID:Immunohistochemical characterization of undifferentiated carcinomas of the ovary. 796 44

Detection of micrometastatic tumor cells in bone marrow of cancer patients has been shown to be of prognostic significance. To further characterize these cells, we combined antibody labeling and fluorescence in situ hybridization (FISH). For detection of numerical changes of chromosome 17, nine patients with proven breast cancer whose bone marrow contained epithelial tumor cells were evaluated. Epithelial cells were stained by anticytokeratin antibody. Afterwards FISH was performed using an alpha-satellite probe specific for chromosome 17. In a second series bone marrow epithelial cells of eight patients with breast cancer and of six with prostatic cancer were evaluated for the amplification of HER-2/neu by using a gene-specific DNA probe. In the first series four patients had only single epithelial cells in their bone marrow. Only one single cell showed five hybridization signals, whereas all other single cells showed two or less. Five patients had clusters of epithelial cells in bone marrow with or without additional single cells. One hundred four cells had three or more hybridization signals and 103 of these polysomic cells were located in tumor cell clusters. In the second series we could detect HER-2/neu amplification in bone marrow epithelial tumor cells in two of eight patients with breast cancer but in none of the prostatic cancer patients. These results show that it is possible to detect numerical chromosomal changes and oncogene amplification in bone marrow micrometastatic epithelial cells of cancer patients by combining immunophenotyping and FISH.
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PMID:Detection of genetic alterations in micrometastatic cells in bone marrow of cancer patients by fluorescence in situ hybridization. 863 Sep 85

Various types of tumors show aberrant expression and overexpression of epidermal growth factor (EGF) receptor and the degree of receptor expression correlates with a malignant phenotype in many epithelial tumors. However, in vitro evidence supporting the advantageous role of receptor overexpression is deficient. In this study, we compared the effects of exogenous EGF on the cell colony morphology in monolayer and collagen gel culture between HSC-1 squamous carcinoma cells overexpressing EGF receptor and their revertant subline cells. These cells formed coherent cell colonies under routine culture conditions, but addition of EGF induced dissociation of cell colonies within 24 h in the parent HSC-1 cells, though not in the subline cells. Since the colony dissociation apparently involved loss of cell-cell adhesion, we also studied the effects of EGF on E-cadherin expression and its function. Cell aggregation assays showed that EGF reduced E-cadherin function dose-dependently in the parent cells, but not in the subline cells. However, immunoblotting analysis and ELISA showed the absence of downregulation or degradation of E-cadherin. Instead, EGF tyrosine phosphorylated cadherin/catenin complex components including beta-catenin and increased the detergent solubility of E-cadherin in the parent cells. These results suggest that EGF modified the functional association between E-cadherin and actin filament through tyrosine phosphorylation of the cadherin/catenin complex and thereby made the adhesion molecule incompetent. Our results indicate that the ligand activation of overexpressed EGF receptor impairs E-cadherin-mediated cell-cell adhesion and causes dissociation of the squamous carcinoma cell colonies, which facilitates tumor cell invasion in vivo. This might be relevant to the advantageous role of EGF receptor overexpression in malignant phenotype of epithelial tumor cells.
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PMID:Ligand activation of overexpressed epidermal growth factor receptor results in colony dissociation and disturbed E-cadherin function in HSC-1 human cutaneous squamous carcinoma cells. 863 95

Laryngeal papilloma (LP) is the most frequent benign laryngeal epithelial tumor caused by human papillomaviruses (HPV) types 6 and 11. In the present study, we were interested in whether we can find any prognostic markers which might reflect the biological behavior of the covering epithelium in LP. We focused our attention on the determination of HPV infection, the detection of p53 protein, and c-erbB-2 protein in 24 biopsy specimens of LP. We confirmed the HPV 6 and 11 etiology in 23 of 24 LP. In these lesions the overexpression of p53 protein increased with the grade of epithelial abnormalities. The distribution of positive cells changed from scattered and focal, in simple and abnormal hyperplasia, to diffuse in atypical hyperplasia. It has been shown that in the presence of HPV types 6 and 11 found in LP, p53 can still preserve its tumor suppressor activity. Infection with HPV types 6 and 11 might therefore account for the significantly lower rate of malignant transformation in LP. Two staining patterns for c-erbB-2 protein were observed in the hyperplastic epithelium covering LP: membranous and cytoplasmic. With the increasing grade of epithelial abnormalities, cytoplasmic staining became predominant, and c-erbB-2 positivity sometimes occupied the whole epithelial thickness. This may represent either an alteration in the processing stability of the c-erbB-2 mRNA, gene amplification, or even an artefact.
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PMID:Human papillomavirus infection and expression of p53 and c-erbB-2 protein in laryngeal papillomas. 919 99

Recently reported morphologic and molecular genetic evidence suggests that some ovarian carcinomas arise from their benign and low malignant potential (LMP) counterparts. In order to help reach a better understanding of ovarian tumorigenesis, we studied a wide range of gene products involved in cellular growth regulation in archival material obtained from three groups of tumors with graduated malignant potential. Immunohistochemical staining was performed for Ki-67, proliferating cell nuclear antigen (PCNA), epidermal growth factor receptor (EGFR), HER-2/neu-encoded receptor protein, p53 gene product, and multidrug resistance gene product (P-glycoprotein). The expression of EGFR, HER-2/neu-encoded receptor protein, and mutant p53 product was significantly lower in LMP tumors than in carcinomas (p < 0.05). HER-2/neu immunopositivity was more prevalent in adenocarcinomas than in LMP tumors, and the proportion of HER-2/neu-positive adenocarcinomas increased with the progression of the disease. The staining differences between LMP tumors and adenocarcinomas with antibodies against Ki-67, PCNA, and P-glycoprotein were not statistically significant. Immunohistochemical detection of EGFR, HER-2/neu, and p53 in ovarian epithelial tumor is relevant to ovarian tumorigenesis. It could serve as a powerful tool for the pursuit of retrospective studies focused on these important biologic markers.
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PMID:Immunohistochemical assessment of proliferation markers and altered gene expression in archival specimens of ovarian epithelial tumors. 939 93

High-dose chemotherapy (HDC) with autologous bone marrow or peripheral stem cell transplantation is discussed as one option to treat the extensive stage of a variety of tumors. Effective methods to eliminate contaminating tumor cells from human bone marrow or stem cell grafts may improve the outcome of the patients. We investigated 3 recombinant bispecific single-chain antibodies (bscAbs) directed against 17-1A (EpCAM), c-erbB-2 (HER-2/neu) and LeY on the one and CD3 on the other binding site for their ability to induce lysis of epithelial tumor cells by retargeting autochthonous T lymphocytes present in bone marrow mononuclear cells (BMMC) and in peripheral stem cell mononuclear cells (PSMC). The bscAbs showed remarkable specific lysis of different epithelial tumor cell lines with BMMCs as well as with PSMCs as effector cells. Investigation of the alpha 17-1A-alpha CD3 bscAb revealed a significant correlation between the percentage of CD3(+) cells present in the BMMCs and the rate of lysis as well as the absence of detrimental effects on the viability of hematopoietic progenitor cells as determined by colony-forming unit assays (CFUs). Our results indicate that recombinant bispecific single-chain antibodies could be new tools for purging of human bone marrow and peripheral stem cell grafts from contaminating epithelial cancer cells for patients receiving autologous stem cell transplantation after HDC.
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PMID:Bispecific single-chain antibodies as effective tools for eliminating epithelial cancer cells from human stem cell preparations by redirected cell cytotoxicity. 1143 7

The phenotypic switching called epithelial-to-mesenchymal transition is frequently associated with epithelial tumor cell progression from a comparatively benign to an aggressive, invasive malignancy. Coincident with the emergence of such cellular plasticity is an altered response to transforming growth factor-beta (TGF-beta) as well as epidermal growth factor (EGF) receptor amplification. TGF-beta in the tumor microenvironment promotes invasive traits largely through reprogramming gene expression, which paradoxically supports matrix-disruptive as well as stabilizing processes. ras-transformed HaCaT II-4 keratinocytes undergo phenotypic changes typical of epithelial-to-mesenchymal transition, acquire a collagenolytic phenotype, and effectively invade collagen type 1 gels as a consequence of TGF-beta1 + EGF stimulation in a three-dimensional physiologically relevant model system that monitors collagen remodeling. Enhanced collagen degradation was coupled to a significant increase in matrix metalloproteinase (MMP)-10 expression and involved a proteolytic axis composed of plasmin, MMP-10, and MMP-1. Neutralization of any one component in this cascade inhibited collagen gel lysis. Similarly, addition of plasminogen activator inhibitor type 1 (SERPINE1) blocked collagen degradation as well as the conversion of both proMMP-10 and proMMP-1 to their catalytically active forms. This study therefore identifies an important mechanism in TGF-beta1 + EGF-initiated collagen remodeling by transformed human keratinocytes and proposes a crucial upstream role for plasminogen activator inhibitor type 1-dependent regulation in this event.
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PMID:TGF-beta1 + EGF-initiated invasive potential in transformed human keratinocytes is coupled to a plasmin/MMP-10/MMP-1-dependent collagen remodeling axis: role for PAI-1. 1938 99

A total of 96 cases of invasive breast ductal carcinoma were examined for immunohistochemical expression of Bax and Bcl-2 in the epithelial tumor cells and endothelial cells of the blood vessels. We also investigated the association between both proteins in the epithelium in relation to tumor characteristics such as tumor size, grade, lymph node involvement, microvessel density (MVD), hormonal receptors expression and c-erbB-2 overexpression. Bax expression showed a significant association between tumor and endothelial cells (p<0.001) while Bcl-2 expression in tumor cells was inversely associated with that in the endothelial cells (p<0.001). Expression of Bcl-2 in tumor cells was strongly associated with expression of estrogen and progesterone receptors (p=0.003 and p=0.004, respectively). In addition, intratumoral MVD was significantly higher than peritumoral MVD (p<0.001) but not associated with Bax or Bcl-2 expression and other tumor characteristics. We concluded that the number of endothelial cells undergoing apoptosis was in direct linkage with the number of apoptotic tumor cells. Anti-apoptotic activity of the surviving tumor cells appears to propagate cancer progression and this was influenced by the hormonal status of the cells. Tumor angiogenesis was especially promoted in the intratumoral region and angiogenesis was independent of anti-apoptotic activity.
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PMID:Expression of Bax and Bcl-2 in tumour cells and blood vessels of breast cancer and their association with angiogenesis and hormonal receptors. 2309 83

Perforin (pfp)-mediated cytotoxicity is one of the principal immunosurveillance mechanisms involved in the fight against cancer. However, its importance in spontaneous epithelial cancer is still poorly defined. In this study, we use a realistic mouse model that displays many features that are equivalent to human pathology to evaluate the role of pfp-dependent immunosurveillance by comparing tumor progression in rat ERBB-2 (neu) transgenic, pfp-proficient (neu(+)/pfp(+)) or pfp-deficient (neu(+)/pfp(-)) BALB/c male mice. Adult neu(+)/pfp(+) males developed poorly differentiated salivary carcinomas, whereas neu(+)/pfp(-) males displayed their salivary carcinomas noticeably earlier and showed zones of more highly differentiated tumor, indicating that pfp-mediated immunosurveillance is able not only to delay the growth kinetic of an aggressive epithelial tumor, but also to shape its histology. The role of pfp-mediated immunosurveillance appeared to be of even more dramatic importance against the less aggressive male mammary carcinomas. In neu(+)/pfp(+) males, the incidence of mammary carcinomas was a sporadic and late event. In contrast, in neu(+)/pfp(-) males their incidence was four-fold higher. This higher cancer incidence was associated with a 2-fold higher occurrence of persisting mammary remnants, a major risk factor for mammary cancer in male mice, and one that would appear to be due to pfp's previously unidentified involvement in male mammary gland rejection during embryogenesis. This work thus provides further proof of the complex role that the immune system plays in the body and gives new insight into the pathogenesis of epithelial tumors, demonstrating that the penetrance and malignancy of a tumor may be dramatically affected by pfp-dependent mechanisms.
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PMID:Multiple roles of perforin in hampering ERBB-2 (Her-2/neu) carcinogenesis in transgenic male mice. 2479 Jan 44


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