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)

Histological and anatomopathological studies performed on 152 independent myeloblastosis-associated virus type 1 (MAV1)-induced nephroblastomas allowed us to precisely define the chronology of tumor development in chickens. Three tumors representing increasing developmental stages were used to construct genomic libraries and to study both the state of proviral genomes and the sites of MAV1 integration in genomic DNA. We established that increasing levels of proviral rearrangement, eventually leading to the elimination of infectious MAV genomes, were associated with tumor progression and that 22 individual tumors, representative of different developmental stages, did not contain any common MAV1 integration site. Cloning of cellular fragments flanking the MAV1-related proviruses in tumor DNA showed that each one of eight nephroblastomas tested expressed a high level of an as yet unidentified cellular gene (nov) whose transcription is normally arrested in adult kidney cells. Cloning of the normal nov gene established that in one tumor, fused long terminal repeat-truncated nov mRNA species were expressed, indicating that at least in that case, the high level of nov expression was under the control of the MAV long terminal repeat promoter. The normal nov gene encodes a putative 32-kDa secreted polypeptide, which is a member of a new family of proteins likely to be involved in cell growth regulation. We also showed that the expression of an amino-terminal-truncated nov product in chicken embryo fibroblasts was sufficient to induce their transformation.
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PMID:Proviral rearrangements and overexpression of a new cellular gene (nov) in myeloblastosis-associated virus type 1-induced nephroblastomas. 130 86

Transforming growth factor-alpha (TGF-alpha) is a polypeptide growth factor that binds to the epidermal growth factor receptor and is though to stimulate cell proliferation. It has been believed to play a role in tumor initiation by inducing the reversible transformed phenotype; overexpression of TGF-alpha may be important for tumor progression via autocrine stimulation and oncogene overexpression. Expression of TGF-alpha and the epidermal growth factor receptor has been documented in several nontumorous tissues and in a variety of tumors. This study used immunohistochemistry to localize TGF-alpha expression in normal and neoplastic endocrine tissues. Transforming growth factor-alpha was found in nontumorous hypothalamus, pituitary, thyroid, parathyroid, adrenal cortex and medulla, and pancreatic islets. Immunoreactivity was detected in most benign and malignant tumors of these tissues, as well as in endocrine neoplasms of the lung and gastrointestinal tract. Hypothalamic gangliocytomas, pheochromocytomas, and adrenal cortical carcinomas showed consistently greater immunoreactivity than their normal counterpart, but there was no correlation between degree of reactivity and tumor grade, stage, or hormone content. These results suggest that in endocrine tissues, TGF-alpha is unlikely to prove useful as a tumor marker but that the growth factor may play a role in both normal physiology and tumorigenesis.
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PMID:Transforming growth factor-alpha in normal and neoplastic human endocrine tissues. 146 72

We have studied the expression of insulin-like growth factor II (IGF-II) during hepatocarcinogenesis in four independent transgenic mouse lines. In all four lines liver-directed transgene expression induces a stepwise and relatively synchronized tumorigenesis. IGF-II reexpression occurs in all four lines irrespective of the mechanism of tumor induction. Reexpression is chronologically associated with late progression steps toward hepatocellular carcinoma and correlated with the respective tumor progression rate in each line. IGF-II activation is focal and topographically associated with high replicative activity. IGF-II mRNAs in hepatocellular carcinomas show similarities to the expression pattern in fetal liver, and a M(r) 15,000 IGF-II polypeptide accumulates intracellularly in distinct cytoplasmic preferentially perinuclear compartments. These data indicate that IGF-II reexpression is a marker for progression to hepatocellular carcinoma and may contribute to hepatocarcinogenesis via an autocrine mechanism.
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PMID:Reactivation of insulin-like growth factor II during hepatocarcinogenesis in transgenic mice suggests a role in malignant growth. 156 24

The expression of cytokeratin (CK) polypeptides was studied in 59 transitional cell carcinomas (TCC) of the urinary tract of different grade and stage. Using a panel of 14 polypeptide-specific monoclonal CK-antibodies we identified immunohistochemically 8 different CKs separately, ie, CKs 4, 7, 8, 10, 13, 14, 18, and 19, while in immunoblotting studies CK5 expression was detected indirectly by using the antibody RCK102, recognizing CK5 + 8. In low-grade TCCs (G1-G2), the CK distribution was comparable to that in normal urothelium, however with a variable expression of CK13 in the different tumors and a uniform distribution of CK7. In higher-grade TCCs (G3), a decrease in CK13 expression was observed, particularly in the areas of muscle invasion. Furthermore, the appearance and increasing expression of CK14 (not present in normal urothelium or G1 TCCs) with higher grade and stage was striking. With tumor progression changes in epitope configurations of CK8 and CK18 were detected, as concluded from immunohistochemical assays with the panel of monoclonal antibodies for each of these two CKs. In extreme cases this resulted in differential staining patterns of the invasive and noninvasive components within one tumor. In 7 of 32 G3 TCCs, some of which showed areas with evident squamous differentiation, a decrease in the expression of CK7 and/or CK8 was seen. We conclude that tumor progression in TCCs is associated with discrete changes of CK expression, which can be detected using monoclonal antibodies.
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PMID:Distribution of cytokeratin polypeptides in human transitional cell carcinomas, with special emphasis on changing expression patterns during tumor progression. 168 41

TPA is a tumor marker characteristic of general cellular proliferation. High serum levels are found in patients with tumor progression. With the aim of bettering the clinical use, the authors have isolated TPA in purer form, in order to develop, in the future, a more specific immunoenzymatic method based on unlabeled antipeptide antibodies. A simple method for the isolation of small amounts of tissue polypeptide antigen (TPA) from the sera of patients suffering from neoplastic diseases is described. The procedure takes advantage of the availability of commercial anti-TPA coated beads; sera pools with high levels of antigen are allowed to react with such beads, then the antibody-antigen complex is dissociated by drastic changes of pH or molarity, and TPA recovered. Such TPA preparations contain low amounts of extraneous proteins, and thus can be utilized in immunoenzymatic tests, or in laboratory investigations.
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PMID:Preparation of tissue polypeptide antigen (TPA) from sera pools of cancer patients. 184 12

High-resolution two-dimensional polyacrylamide gel electrophoresis (PAGE) was employed to reveal tumor-associated polypeptide changes, using the BALB/c C4 line mouse mammary model system, for which phenotypic and immunogenic alterations accompanying tumor progression are well defined. In the first set of experiments, polypeptide patterns from 20 micrograms whole tissue lysates of normal mammary gland, C4 preneoplastic hyperplastic alveolar nodule outgrowth (HAN) and spontaneous tumor from C4 HAN were compared. In order to normalize for differential cellularity and extracellular protein content in the whole tissues, our analysis included polypeptide patterns from serum, increased concentration of protein from whole normal mammary gland, and primary cultures of epithelial cells from normal gland, HAN and tumor. Using a computer-based image-analysis system, 90 polypeptides were identified in C4 tumor that were absent in C4 HAN, normal mammary gland and serum. None of the 90 polypeptides could be shown to represent a definite qualitative change in the protein composition of tumor epithelium as they were found to be either present in a higher concentration of protein from whole normal gland, or present in the primary epithelial culture from HAN, or absent in the primary epithelial culture from tumor. Conversely in the second set of experiments, when epithelial cultures were used as the starting point for comparisons to locate tumor-associated polypeptides, none of the 15 polypeptides that were present in cultures from three different tumors, and absent in the culture from normal mammary gland was specific to C4 tumor, as they were present in whole tissues of normal gland. Thus our experimental approach detected significant quantitative but no qualitative polypeptide changes in whole tumor tissue, or in tumor-derived epithelial cell cultures. This finding may reflect the limitations of the two-dimensional PAGE method, and warrants caution in the use of such gel analysis alone to identify tumor-associated proteins.
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PMID:Two-dimensional gel analysis of polypeptides from normal, preneoplastic and neoplastic mouse mammary tissues. 230 27

NKI/C-3 and NKI/black-13 are monoclonal antibodies recognizing different epitopes on a melanoma-associated antigen that is preserved after fixation in formalin and embedding in paraffin in virtually all melanoma tissues. The antigen, a predominantly cytoplasmic vesicle membrane-bound heterogeneous glycoprotein of 25-110 X 10(3) daltons, was shown to be a single 25 X 10(3) dalton polypeptide when incorporation of N-linked carbohydrates was inhibited by tunicamycin. The antigen was measured in a double determinant enzyme immunoassay (DDEIA) using NKI/C-3 as catcher antibody. Results from in vitro experiments indicated that the antigen is actively shed from living cells. In sera from melanoma patients with a small tumor burden, the antigen concentrations were in the range of those of controls (0-22 U/ml). Significantly increased values (33-600 U/ml) were found in sera from patients with a moderate or large tumor burden. The antigen concentrations in sera from patients with multiple metastases of other tumors were within the range of controls. Several sera from patients with multiple metastases of colon, pancreatic, and stomach carcinoma, however, contained increased antigen concentrations (45-80 U/ml). These results correspond with the reactions of NKI/C-3 in tissue sections of some malignancies other than melanoma. During the follow-up of melanoma patients the concentrations of circulating antigen correlated with tumor progression. The predictive value of the NKI/C-3 assay was no better than determination of serum lactate dehydrogenase, alkaline phosphatase or gamma glutamyl transferase activity.
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PMID:Circulating melanoma-associated antigen detected by monoclonal antibody NKI/C-3. 243 Jul 6

In our previous report, monoclonal antibody PR92 has defined prostate- and breast tumor-associated PR92 antigen. The molecular nature of PR92 antigen, especially the epitope involved in specific interaction with PR92 monoclonal antibody, is described. PR92 antigen was purified from the cell extract or tissue culture medium of prostate cancer cell line DU145 by means of monoclonal antibody-coupled Sepharose 4B affinity chromatography, followed by a Sephacryl S-500 chromatography. Physical and chemical characterization, coupled with high-performance liquid chromatography, determined that PR92 antigen is a glycoprotein with a molecular weight of about 470,000, comprising repeating subunits of about 44,000. Sialic acid was found to form a critical part, while D-galactose and N-acetylgalactosamine were also involved, in the epitope structure. PR92 antigen is rich in serine, threonine, proline, glycine, and alanine and poor in aromatic amino acid residues. The carbohydrate moieties may be predominantly O-linked to polypeptide chains which contribute directly or indirectly to maintain the integrity of the epitope. Elucidation of the molecular nature of PR92 antigen may help understand the mechanism of shedding into the body fluids during tumor progression.
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PMID:Molecular characterization of the epitope in prostate and breast tumor-associated PR92 antigen. 246 8

The keratins and other cytoskeletal proteins expressed by normal, preneoplastic, and malignant mammary tissues in BALB/c mice and by cells in primary cultures established from these tissues were analyzed and compared. The preneoplastic lesions were hyperplastic alveolar nodules (HAN) derived originally from mice treated by hormonal stimulation (D2), exposed to a chemical carcinogen (C4), or spontaneously expressing mouse mammary tumor virus (CV2) and maintained by serial transplantation. All tumors were mammary adenocarcinomas which developed as primary neoplasms from the HAN outgrowth lines. Cytoskeletal extracts were prepared from the tissues and cultured cells and subjected to two-dimensional polyacrylamide gel electrophoresis. Comparison of the major polypeptides in the normal and abnormal tissue extracts revealed considerable similarities in the cytoskeletal profiles. Three basic and seven acidic polypeptides ranging in molecular weight from 40,000 to 90,000 were regularly identified. However, notable differences were also found. A Mr 55,000 keratin (IEF 55) was prominent in one HAN, the D2, and all tumor tissues but not in normal gland. Likewise, a Mr 46,000 polypeptide (IEF 46), which has been tentatively identified previously as a keratin, was absent in normal epithelium but present in all abnormal tissues except the C4 and CV2 HAN. A Mr 58,000 polypeptide (NEPHGE 58) was not detected in normal gland or the C4 lesions but was found in all other abnormal tissues. The overall pattern of polypeptides in cytoskeletal extracts from normal and abnormal mammary cells in primary culture resembled that of the corresponding tissue but also had important differences. In all cell cultures, IEF 46 and IEF 55 were major species, while the larger and more basic components were markedly reduced. A Mr 56,000 polypeptide (NEPHGE 56) was detected only in C4 HAN and C4 and CV2 tumor cells. Trace or small, variable amounts of a Mr 57,000 basic keratin (NEPHGE 57) were present in normal and D2 tissues and cultured cells. NEPHGE 57 was dramatically increased in C4 and CV2 tissues and cultured cells and may be related to expression of squamous metaplasia and keratinization which are characteristic of these lesions. Although production of IEF 46 and IEF 55 may be associated with neoplastic progression of mammary epithelium, particularly in vivo, the association is not exclusive since normal cells express these polypeptides when grown in primary culture. In addition, correlations between altered keratin expression and the mode of induction of the mammary lesions were not obvious.
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PMID:Heterogeneity of keratin expression in mouse mammary hyperplastic alveolar nodules and adenocarcinomas. 258 Jun 27

The modulation of gap junctional intercellular communication (GJIC) plays an important role during tumor promotion. Several tumor-promoting agents are known to inhibit this form of cellular coupling. In addition, tumor cells and cells expressing certain oncogenic products have been shown to exhibit inhibited or reduced GJIC. The Ha-ras oncogene is expressed in a wide variety of human tumors from different tissues. Its p21 product is a membrane-bound polypeptide, the function of which is not fully characterized. We tested the effects of the expression of the human c-Ha-ras-1 oncogene, derived from the EJ/T4 bladder carcinoma cell line, on the ability of the Chinese hamster V79 cells to conduct gap junctional communication. The junctional competence was studied by two different methods, the scrape-loading/dye transfer technique and the metabolic cooperation assay. The results indicate a strong correlation between the expression of p21 ras protein and the inhibition of gap junctional function. Assuming that reversible inhibition of intercellular communication plays a role during tumor promotion and stable inhibition during the tumor progression phase of carcinogenesis, our data suggest that, while chemical tumor promoters and the ras oncogenes might work by different biochemical mechanisms, they both affect a critical cellular function; namely, GJIC.
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PMID:Potential role of the human Ha-ras oncogene in the inhibition of gap junctional intercellular communication. 267 3


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