Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MUC1 mucin is found in a variety of epithelial tissues and is overexpressed in several epithelial cancers. This molecule could modulate cellular adhesion and thereby influence tumor invasion and metastasis. Little is known of MUC1 gene expression in thyroid tissues. We investigated whether MUC1 mucin gene alteration and/or expression correlated with thyroid tumor progression by studying 21 fresh thyroid tissue specimens comprising 10 macrofollicular adenomas and 11 papillary carcinomas. Normal adjacent tissue from the same patients was also studied. To determine the integrity and expression of the MUC1 mucin gene, a complementary DNA (cDNA) probe was used for Southern blot analysis of DNA and Northern blot analysis of RNA. A detailed immunohistochemical analysis of MUC1 protein expression was performed with DF3 monoclonal antibody, and was compared with other tumor characteristics and clinical manifestations at diagnosis. Of the 14 tumors informative (heterozygous) with the pMUC10 polymorphic probe, 2 (14%) showed loss of heterozygosity (1 adenoma and 1 carcinoma). Overexpression of MUC1 RNA, compared with normal thyroid tissue, was observed in 6 of the 11 papillary carcinomas and in none of the 10 adenomas. Immunostaining of the corresponding formalin-fixed paraffin-embedded tissue sections detected MUC1 mucin protein at the apical domain of follicular cells. Most of the lining was thin in normal tissue and follicular adenomas, but the protein was more irregularly and less strongly expressed in adenomas. In carcinomas the epithelial mucin produced by the MUC1 gene was present irregularly as a thin and/or thick lining at the apical domain of tumor cells. In addition, 5 of the 6 samples with MUC1 mRNA overexpression showed intracytoplasmic staining. Moreover, intracytoplasmic MUC1 mucin staining was found in 75% of "high-risk" papillary thyroid carcinoma (PTC) (PTC with extrathyroid extension at initial diagnosis and/or lymph node involvement), and in only 28.5% of "low-risk" PTC (purely intrathyroidal carcinomas).
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PMID:MUC1 mucin gene, transcripts, and protein in adenomas and papillary carcinomas of the thyroid. 934 75

Mucins are high molecular weight glycoproteins which are heavily glycosylated with many carbohydrate side chains. In epithelial cancers such as colorectal cancer, both qualitative and quantitative alterations in carbohydrate and polypeptide moieties of mucin glycoproteins occur. These changes in mucin glycoproteins are one of the most common phenotypic markers of colorectal carcinogenesis and may play an important pathobiological role. The expression of some of the sialylated carbohydrate antigens appears to correlate with a poor prognosis and increased metastatic potential in colorectal cancer. The increased exposure of peptide epitopes of mucin glycoproteins in colorectal cancer appears to be due to either abnormal glycosylation and/or altered levels of mucin gene transcription. In addition, dysregulation of tissue specific mucin genes occurs in colorectal cancers. This information is currently being exploited for further elucidation of the molecular mechanisms involved in carcinogenesis, tumor progression and metastasis, and the development of novel methods of colorectal cancer diagnosis and therapy.
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PMID:Mucin glycoproteins in colonic neoplasia. 956 May 27

The monoclonal antibody UN1 was previously produced in our laboratory on the basis of selective reactivity with human thymocytes and has been classified as unclustered by the 5th and 6th International Workshop and Conference on Human Leukocyte Differentiation Antigens. The antigen recognized by mAb UN1 was found to be expressed on the cell surface of immature human thymocytes, a subpopulation of peripheral T lymphocytes and on several fetal tissues including thymus. The UN1 antigen is purified from children's thymus by ion-exchange and affinity chromatography. Two-dimensional electrophoresis shows that the purified antigen displays microheterogeneity appearing as multiple spots over a pI range 4.4-5.0 at 100-120 kDa. Treatment with neuraminidase results in a retarded migration in SDS-PAGE, an increase in isoelectric point and a reduction in carbohydrate content, indicating a substantial content of sialic acid. Glycosidase digestion and lectin-binding analysis indicate that the carbohydrate residues are essentially O-linked. A preliminary analysis has detected the UN1 antigen in human breast carcinoma tissues but not in normal breast. The biochemical features and the pattern of expression of the UN1 antigen indicate that this molecule may have the characteristics typical of the family of cell-membrane-associated mucin-like glycoproteins; a number of these molecules are thought to have a role in cell-cell interaction, tumor progression and metastasis.
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PMID:Purification and characterization of a human sialoglycoprotein antigen expressed in immature thymocytes and fetal tissues. 967 51

Molecular changes associated with breast cancer progression were characterized using the MCF-10F cell series. MCF-10F was established from fibrous mastectomy tissue of a patient without detectable cancer. In vitro treatment of MCF-10F cells with benzo(a)pyrene resulted in a transformed subclone MCF-10F-BP1 (BP1). Transfection of clone BP1 with T24-Hras resulted in the tumorigenic line MCF-10F-BP1-Tras (BP1-Tras). Using flow cytometry, the expression of HLA I, ERBB-2 and MUC-1 was found to be comparable in 'normal' MCF-10F, transformed BP1 and tumorigenic BP1-Tras cells. Glycosylated mucin is elevated in BP1 but reduced in BP1-Tras cells. Using mRNA differential display analysis, cDNA profiles of the 'normal', transformed and tumorigenic cell lines were strikingly similar, yet distinct and elevated expression of several common cDNA fragments was detected in BP1 and BP1-Tras when compared with MCF-10F cells. These fragments were cloned and sequenced. The sequences of clones T1-360 and C4-310 are homologous to two reported EST cDNA clones from human fetal tissue and were further characterized. Elevated expression of the genes corresponding to clones T1-360 and C4-310 was verified using Northern blotting. High-level expression of these genes was also detected in the breast cancer cell line MCF-7 that was derived from the pleural effusion of a patient with advanced breast cancer. Therefore, specific molecular changes associated with breast cancer development were identified and may be indicators of neoplastic progression.
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PMID:Neoplastic progression of breast epithelial cells--a molecular analysis. 968 93

Based on the multistage and multifocal nature of colorectal carcinogenesis, it is likely that reduction of cancer mortality through early detection and identification of new prognostic markers is an attainable goal. Well-documented changes occur in mucin glycoconjugates during neoplastic progression in the colon, and the nonneoplastic colonic mucosa in colon cancer patients is morphologically and histochemically abnormal. In this retrospective study, 152 archival colorectal tissues from 49 patients were studied for changes in mucin secretions as detected by the galactose oxidase-Schiff's (GOS) sequence. Intensity of the stain was evaluated in histological sections by semiquantitative analysis, and the area percentage of epithelium stained was quantified by image cytometry. The correlation between gender or tumor size, location and reactivity with peanut agglutinin and quantitative expression of GOS-reactive mucins was determined as well as intratumor and inter individual variability. Reactivity with GOS: (a) decreased during neoplastic progression and malignant conversion in the neoplasm; (b) increased in the normal colonic mucosa of patients with progressively more advanced disease; and (c) was of prognostic significance for patient survival or recurrence both in the normal colon of cancer patients and in invasive neoplasms. These data are consistent with the conclusion that GOS reactivity in the normal colonic mucosa is a dosimeter of exposure to environmental/lifestyle colorectal carcinogens rather than a marker for an oncodevelopmental cancer-associated antigen.
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PMID:Validation of the galactose oxidase-Schiff's reagent sequence for early detection and prognosis in human colorectal adenocarcinoma. 981 34

The most common clinical form of lung cancer is a disseminated disease with distant metastases; several years of cancer progression precede presentation, and this ultimately limits the efficacy of curative therapy. In this immunohistochemical study, we examined a mucinous adenocarcinoma cell line, maintained by xenogeneic transplantation, and a spontaneous metastatic variant which produces distant tumors (in liver, spleen and kidney). The aim was to investigate possible parameters which characterize the metastatic process. Histopathological comparison between the two subcutaneous transplanted tumor lines showed that both lines presented a similar cellular morphology, a different pattern of cellular growth and an increased vascularization in the metastatic line with respect to its parent. All the tumor sections expressed differential immune reactivity with monoclonal antibodies against Lewis y (MAb C14), sialyl-Lewis x (MAb SNH3) and Lewis x (MAb FH2) determinants. Neither expressed MUC 1 mucins detectable with monoclonal antibodies reactive with the mucin protein core (MAbs C595 and SM3) nor was carcinoembryonic antigen (MAb C365) expressed. Neoplastic cells were reactive with an anti-pan cytokeratin monoclonal antibody confirming their epithelial histogenesis. Our findings have been evaluated with respect to defining metastatic phenotypes in lung cancer by examination of distinct histopathological and immunological parameters.
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PMID:Immunohistopathological characterizatin of spontaneous metastases in a human lung mucoepidermoid adenocarcinoma (HLMC) xenograft. 988 55

Sialomucin complex (SMC) is a large heterodimeric glycoprotein complex composed of a mucin subunit ascites sialoglycoprotein-1 and a transmembrane subunit ascites sialoglycoprotein-2. It is a rat homologue of human mucin gene MUC4 and is abundantly expressed on the cell surface of highly metastatic ascites 13762 rat mammary adenocarcinoma cells. Because of their extended and rigid structures, mucin-type glycoproteins are suggested to have suppressing effects on cell-cell and cell-matrix interactions. During the metastatic process, these effects presumably cause tumor cell detachment from the primary tumor mass and facilitate escape of the tumor cells from immunosurveillance. Analyses of human breast cancer cells in solid tumors and tumor effusions showed that the more aggressive cells in effusions are stained with polyclonal antibodies against SMC more frequently than cells in solid tumors, suggesting a role for MUC4/SMC in tumor progression and metastasis. Previously, we generated recombinant cDNAs for SMC that vary in the number of mucin repeats to study the putative functions of SMC in tumor metastasis. These cDNAs were transfected into human cancer cell lines and tested for the effect of the expression of this gene. Here, using a tetracycline-responsive inducible expression system, we demonstrate that overexpression of SMC masks the surface antigens on target tumor cells and effectively suppresses tumor cell killing by cytotoxic lymphocytes. This effect results from the ability of SMC to block killer cell binding to the tumor cells and is dependent on both overexpression of the mucin and the number of mucin repeats in the expressed SMC. These results provide an explanation for the proposed role of SMC/MUC4 in tumor progression.
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PMID:Overexpression of sialomucin complex, a rat homologue of MUC4, inhibits tumor killing by lymphokine-activated killer cells. 1023 13

Villous tumors are rare and their histological diagnosis from biopsy specimens is often difficult. To ascertain its tumor progression, including the genetic events, would be useful for clinical treatment. Clinicopathological features and the expression of p53 and bcl-2 proteins were investigated in 50 villous tumors from 49 patients. The patients' ages ranged widely from 32 to 84 years (average, 61 years). Females were more frequently affected than males (male:female ratio, 20:29). Thirty-six (72%) of the villous tumors were present within the sigmoid colon and rectum. Histologically, 17 (34%) of these contained carcinomas in villous adenomas (CIVA), while 24 (73%) of 33 villous adenomas (VA) contained high-grade dysplasia. Most of the CIVA revealed well-differentiated adenocarcinoma, often with focal or diffuse mucin pools. Three lesions of invasive carcinomas were composed of extremely well-differentiated components. The average size of the CIVA (79 mm) was significantly larger than that of the VA (51 mm). Overexpression of p53 protein was recognized in 12% of VA, in 24% of mucosal components of CIVA and in 18% of invasive components of CIVA. Overexpression of bcl-2 was recognized in 57% of VA, 33% of mucosal components of CIVA, and 7% of invasive components of CIVA. Several characteristic features were recognized in villous tumors, which comprised: (i) a high frequency of coexistence of carcinoma; (ii) multiple foci of carcinomas arising in adenomatous tumors; (iii) a lower histological grade of carcinomas, often with mucin pools; (iv) the existence of extremely well-differentiated adenocarcinomas; and (v) less frequent expression of p53 protein in the carcinomatous components. According to these findings, the pathway of tumor progression in the villous tumors is possibly different from that of sporadic colorectal carcinomas. Because of the peculiarity of villous tumors, careful clinical management is required.
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PMID:Villous tumor of the colon and rectum with special reference to roles of p53 and bcl-2 in adenoma-carcinoma sequence. 1041 79

Mucins are high molecular weight glycoproteins which are heavily glycosylated with many carbohydrate side chains. In epithelial cancers such as biliopancreatic cancer, both quantitative and qualitative alterations in carbohydrate and polypeptide moieties of mucin glycoproteins occur. These changes in mucin glycoproteins are one of the most common phenotypic markers of biliopancreatic carcinogenesis and may play an important pathobiological role. The expression of some of the sialylated carbohydrate antigens appears to correlate with a poor prognosis and increased metastatic potential in biliopancreatic cancer. The increased exposure of peptide epitopes of mucin glycoproteins in biliopancreatic cancer appears to be due to either abnormal glycosylation and/or altered levels of mucin gene transcription. In addition, dysregulation of tissue specific mucin gene expression occurs in biliopancreatic cancer. This information is currently being exploited for further elucidation of the molecular mechanisms involved in carcinogenesis, tumor progression and metastasis, and the development of novel methods of diagnosis and therapy of biliopancreatic cancer.
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PMID:Mucin gene and antigen expression in biliopancreatic carcinogenesis. 1043 85

Furan cholangiocarcinogenesis in rat liver is proving to be a unique and useful animal model for investigating important aspects of the cellular and molecular pathogenesis of cholangiocarcinoma potentially relevant to the human disease. We now describe the first culture model of rat cholangiocarcinoma cells derived from a transplantable cholangiocarcinoma originally induced in the liver of a furan-treated rat. An epithelial cell isolate highly enriched in viable cholangiocarcinoma cells was consistently obtained from transplantable cholangiocarcinoma tissue utilizing a similar procedure to that recently developed by us to establish a new rat hyperplastic bile ductular epithelial cell culture model characterized by the appearance of polarized bile ducts in vitro. Primary cholangiocarcinoma cell cultures could be readily established with these isolated cells and, in addition, we established from one such culture a novel rat cholangiocarcinoma cell line designated C611B. Cultured C611B cholangiocarcinoma cells retained a number of important characteristic features of the carcinoma cells of the parent tumor, including marked expression of the tyrosine kinase growth factor receptor proteins c-Met and c-Neu. Under basal culture conditions, the C611B cell line exhibited a cell doubling time of approximately 24 h and was aneuploid, with a predominant chromosomal count of 43. Moreover, C611B cells on collagen gels were 100% tumorigenic when transplanted into inguinal fat pads of syngeneic rats. All tumors formed at the transplantation site were cytokeratin 19-positive, mucin-producing tubular adenocarcinomas whose histological and phenotypic features closely resembled those of the furan-induced parent transplantable rat cholangiocarcinoma. Based on our findings, we believe that this novel rat cholangiocarcinoma cell culture model can serve as a valuable resource for investigating aberrant growth properties and tumor progression in biliary cancer.
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PMID:Establishment of a novel rat cholangiocarcinoma cell culture model. 1059 Feb 29


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