Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transformed mouse epidermal keratinocytes of the cell line PDV, when cultured under the presence of transforming growth factor-beta 1 (TGF-beta 1), escaped the block of growth exerted by this factor in normal keratinocytes and underwent marked changes in cell differentiation. TGF-beta 1 induced disruption of epithelial interactions, dispersion of cells, increased local movement, and conversion to a fibroblast-like morphology. These changes were reversible and correlated with down-regulation of epithelial protein markers such as E-cadherin and cytokeratins and upregulation of vimentin. TGF-beta 1-treated cells with a fibroblast-like phenotype induced spindle cell carcinomas upon transplantation in athymic nude mice, whereas untreated PDV cells or fusiform cells reverted to the epithelial phenotype and produced well-differentiated squamous cell carcinomas. Nontumorigenic immortalized epidermal keratinocytes, when grown under the presence of TGF-beta 1, did not transdifferentiate to a mesenchymal phenotype, their proliferation was blocked, and cells finally died. These results suggest a role of TGF-beta 1 in the progression of squamous carcinoma cells to spindle carcinomas in mouse skin carcinogenesis.
 ...
PMID:Chronic exposure of cultured transformed mouse epidermal cells to transforming growth factor-beta 1 induces an epithelial-mesenchymal transdifferentiation and a spindle tumoral phenotype. 854 17

Disturbed function of E-cadherin and/or of one of its anchoring proteins, the catenins, is thought to destabilize E-cadherin-mediated cell-cell adhesion, which may enhance the invasiveness of epithelial cells and thus favor carcinoma progression. Reduced expression of E-cadherin and alpha-catenin, as well as mutations in the E-cadherin gene, have been found in various carcinomas, whereas mutations in the alpha- and beta-catenin genes have been described only in carcinoma cell lines. Using reverse transcription-PCR, followed by agarose gel electrophoresis and single-strand conformational polymorphism, we examined 16 diffuse- and 5 intestinal-type gastric carcinomas, as well as 9 lobular and 2 ductal breast carcinomas, for mutations of alpha- and beta-catenin cDNA. All of the investigated tumors were analyzed previously for E-cadherin mutations. Comparing tumorous and nontumorous samples, we detected neither deletions nor aberrant single-strand conformational polymorphism patterns. At nucleotide 2220 of the alpha-catenin gene, we identified one frequent polymorphism. Our findings suggest that, in contrast to E-cadherin, mutations of alpha- and beta-catenin do not contribute to the pathogenesis or the diffuse growth patterns of gastric or breast carcinomas.
 ...
PMID:No evidence for mutations in the alpha- and beta-catenin genes in human gastric and breast carcinomas. 854 73

The HaCa4 cell line, derived from a mouse skin carcinoma induced by Harvey murine sarcoma virus, is highly tumorigenic when injected into nude mice and produces multiple metastases in the lungs. HaCa4 cells express high levels of viral Ha-ras oncogene products, anomalously synthesize the embryonic/simple epithelial keratin K8, and have lost the expression of the cell-cell adhesion receptor E-cadherin (E-CD). E-CD(+) cell clones (E62 and E24), obtained by transfection of an exogenous E-CD cDNA into HaCa4 cells, had a decreased ability to migrate through type IV collagen matrices. However, the E-CD (+) E62 clone remained as metastatic as the parental cell line, whereas the E24 clone, which does not take up the exogenous cDNA but spontaneously switches on the endogenous E-CD gene, suppressed the metastatic phenotype although it maintained its tumorigenicity. E24 cells had fivefold to sixfold lower levels of viral Ha-ras mRNA and p21 protein than the other cell lines. In addition, they did not synthesize K8 but rather switched on keratin K19. The comparison of E-CD proteins synthesized by E62 and E24 cell lines revealed no structural or functional differences because both localized at cell-cell contacts and associated with alpha-catenin, beta-catenin, and plakoglobin. Furthermore, E-CD was still expressed in metastatic lung nodules produced by E62 cells. These results suggest that suppression of the metastatic phenotype in E24 cells occurs independently of E-CD expression and correlates with decreased levels of the oncogenic ras p21 protein.
 ...
PMID:Suppression of the metastatic phenotype of a mouse skin carcinoma cell line independent of E-cadherin expression and correlated with reduced Ha-ras oncogene products. 859 77

E-cadherin (E-cad) is a calcium-dependent, epithelial cell adhesion molecule whose reduced or lost expression has been associated with tumor dedifferentiation and increased metastatic potential in human carcinomas. The authors studied immunohistochemically E-cad expression in frozen sections of 362 breast carcinomas using a monoclonal antibody (HECD-1). The immunohistochemical detection of reduced E-cad expression was confirmed by mRNA in situ hybridization with two different oligonucleotide probes. THe proportion of tumors with reduced or lost E-cad expression increased significantly from pure intraductal carcinomas (20%, 4 of 20) through invasive ductal (IDCs; 52%, 124 of 239) to recurrent carcinomas (64%, 18 of 28; chi square test for trend, P = .004). Invasive lobular carcinomas (ILCs) and IDCs differed from each other in their E-cad expression. None of the ILCs (n=55) retained normal E-cad expression in contrast to 48% (115 of 239) of the IDCs. In 259 primary IDCs, reduced E-cad expression was associated with high histologic grade (chi square test for trend, P < .001), negative estrogen receptor status (ER; Fisher's exact test; P = .042), and marginally with axillary node involvement (Fisher's exact test, P = .063). In a subset of 109 primary IDC patients whose clinical follow-up was available (median follow-up 51 months), reduced E-cad expression was associated with shortened disease-free survival (DFS; Mantel-Cox test, P = .027). In Cox's multivariate regression analysis, progesterone receptor status (P = .018) and E-cad expression (P = .072) were selected as independent predictors of DFS. Our findings provide clinical evidence that loss of normal E-cad expression is an indicator of increased invasiveness and dedifferentiation in breast carcinoma. E-cad is a potentially important prognostic factor in primary IDCs.
 ...
PMID:Reduced E-cadherin expression is associated with invasiveness and unfavorable prognosis in breast cancer. 860 81

There is a need to establish animal models which are suitable for investigation of human gastric cancer metastasis to the liver. To this end, a human gastric carcinoma line, AZ521 was injected into the spleens of nude mice. Cells from the few liver metastatic foci of injected AZ521 were expanded "in vitro" and subsequently injected into the spleens of nude mice. By repeating these procedures three times, we were able to obtain a cell line, designated as AZ-H3c, with high metastatic potential in nude mice. Liver metastasis developed in 15 of 21 (71%) animals injected with AZ-H3c, but only in 14% of those injected with parental AZ521. Further, AZ-H3c caused faster tumor development than did AZ521. However, the primary AZ-H3c tumors and liver metastatic AZ-H3c tumors showed essentially the same histological appearance. We also analyzed the cell surface expression of adhesion molecules. The data showed that the expression of VLA-1, VLA-2, VLA-3, VLA-4, VLA-5 was enhanced in AZ-H3c. In contrast, the expression of VLA-6, (alpha(v)beta3), E-cadherin, ICAM-1 and LFA-1 was reduced in this high-metastatic line. These results suggest that (beta1) integrins play an important role in the liver metastasis of human gastric carcinoma cells. Our high-metastatic line should be useful for studies aimed at the prevention of liver metastasis.
 ...
PMID:Establishment and characterization of human gastric carcinoma lines with high metastatic potential in the liver: changes in integrin expression associated with the ability to metastasize in the liver of nude mice. 860 64

Plakoglobin is the only protein that occurs in the cytoplasmic plaques of all known adhering junctions and has been shown to be crucially involved in the formation and maintenance of desmosomes anchoring intermediate-sized filaments (IFs) by its interaction with the desmosomal cadherins, desmoglein (Dsg), and desmocollin (Dsc). This topogenic importance of plakoglobin is now directly shown in living cells as well as in binding assays in vitro. We show that, in transfected human A-431 carcinoma cells, a chimeric protein combining the vesicle-forming transmembrane glycoprotein synaptophysin, with the complete human plakoglobin sequence, is sorted to small vesicles many of which associate with desmosomal plaques and their attached IFs. Immunoprecipitation experiments have further revealed that the chimeric plakoglobin-containing transmembrane molecules of these vesicles are tightly bound to Dsg and Dsc but not to endogenous plakoglobin, thus demonstrating that the binding of plakoglobin to desmosomal cadherins does not require its soluble state and is strong enough to attach large structures such as vesicles to desmosomes. To identify the binding domains and the mechanisms involved in the interaction of plakoglobin with desmosomal cadherins, we have developed direct binding assays in vitro in which plakoglobin or parts thereof, produced by recombinant DNA technology in E. coli, are exposed to molecules containing the "C-domains" of several cadherins. These assays have shown that plakoglobin associates most tightly with the C-domain of Dsg, to a lesser degree with that of Dsc and only weakly with the C-domain of E-cadherin. Three separate segments of plakoglobin containing various numbers of the so-called arm repeats exhibit distinct binding to the desmosomal cadherins comparable in strength to that of the entire molecule. The binding pattern of plakoglobin segments in vitro is compared with that in vivo. Paradoxically, in vitro some internal plakoglobin fragments bind even better to the C-domain of E-cadherin than the entire molecule, indicating that elements exist in native plakoglobin that interfere with the interaction of this protein with its various cadherin partners.
 ...
PMID:The binding of plakoglobin to desmosomal cadherins: patterns of binding sites and topogenic potential. 860 68

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.
 ...
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

We examined the expression of E-cadherin and collagenase type IV in formalin-fixed, paraffin-embedded specimens of human gastric carcinoma by an in situ mRNA hybridization (ISH) technique. The ISH technique revealed intertumoral heterogeneity for expression of E-cadherin and collagenase among 12 cases of early gastric cancer and 13 cases of advanced gastric cancer. In the majority of the tumors, we found an inverse relationship between the reactivities of E-cadherin and collagenase type IV. Specifically, E-cadherin was expressed at higher levels in the center of the neoplasms than in their periphery, whereas collagenase type IV was expressed at a higher level in the periphery (invasive edge) than in the center. Advanced gastric cancers with high levels of expression for collagenase type IV in the periphery had a higher incidence of distant lymph node metastasis than those with low expression. The data show an inverse relationship between E-cadherin (involved in cell-to-cell adhesion) and collagenase type IV (involved in invasion) in different zones of human gastric carcinoma and suggest that the relative expression of these independent genes may be involved in local invasion and metastasis.
 ...
PMID:Intratumoral heterogeneity and inverse correlation between expression of E-cadherin and collagenase type IV in human gastric carcinomas. 864 46

Using specific ELISA kits, we investigated the secretion of cytokines in five human prostate carcinoma cell lines: ALVA 31, DU145, LNCaP, ND1 and PC3. Three of the five cell lines investigated secreted granulocyte-macrophage colony-stimulating factor (GM-CSF); GM-CSF was not identified in ALVA31 or LNCaP. In addition, we have shown that conditioned media of DU145, ND1 and PC3 stimulated proliferation of the GM-CSF-dependent cell line MO7e indicating that these cells secrete biologically active GM-CSF. By flow cytometric analysis we determined that all five cell lines expressed the alpha-subunit of the GM-CSF receptor on the cell surface but only ALVA31 expressed both the alpha- and beta-subunits of the GM-CSF receptor. Varying concentrations of GM-CSF did not stimulate the proliferation rate of any of the prostate carcinoma cell lines. Thus, there does not appear to be autocrine loop of GM-CSF-induced proliferation. However, the expression of E-cadherin and endoglin (CD105) was modulated under GM-CSF treatment in ALVA31. In addition, GM-CSF decreased the level of soluble CD44 in ND1. These results suggest that the GM-CSF receptor alpha-subunit may play a role in metabolic activity of prostate cancer.
 ...
PMID:Human prostate carcinoma cell lines secrete GM-CSF and express GM-CSF-receptor on their cell surface. 868 98

The effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) and benzoyl peroxide (BoP) on gap junctional intercellular communication (GJIC) and the amount and localization of E-cadherin was studied in initiated mouse epidermal cells (3PC) and in carcinoma cells (CA3/7) originating from the same cell type. In addition, the localization and phosphorylation of connexin43 was studied in both cell lines and in primary keratinocytes. GJIC inhibition by TPA and BoP was stronger in primary keratinocytes compared with both cell lines. BoP strongly decreased the amount of E-cadherin protein and the level occurring in the membranes in both cell lines, whereas TPA caused a translocation of E-cadherin from the membrane towards the cytosol, without decreasing the total amount of E-cadherin present. The effect of both tumor promoters on connexin43 phosphorylation and localization was agent as well as cell dependent. These results show for the first time that tumor promoters can decrease the quantity and membrane localization of E-cadherin in different cell types.
 ...
PMID:Inhibition of gap junctional intercellular communication and delocalization of the cell adhesion molecule E-cadherin by tumor promoters. 870 59


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>