Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human colonic cell line PC/AA, derived from an adenoma, retains in vitro colonic cell differentiation, notably the production of mucus glycoproteins. The PC/AA adenoma cells produce an extracellular gel layer in culture. The PC/AA gel could be isolated by extraction of the cell cultures with guanidine hydrochloride. The extracted material was purified by gel filtration and caesium chloride density-gradient centrifugation and showed properties typical of mucus glycoproteins, namely, a carbohydrate content above 60% of dry weight rich in N-acetylgalactosamine and sialic acid and low in mannose; an amino acid composition with high serine threonine and proline content; a molecular weight above 1,000 kDa on Sepharose CL 4B chromatography and on SDS-polyacrylamide gel electrophoresis under reducing conditions (greater than 200 kDa); a buoyant density of approximately 1.48 g/ml and the release of oligosaccharides by the alkaline beta-elimination reaction. Comparison of the gel mucus glycoprotein purified from premalignant PC/AA cells with normal human colon mucin showed that it has a higher sialic acid content. This suggests that higher sialic acid levels may precede the development of malignancy.
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PMID:Characterization of a sialic-acid-rich mucus glycoprotein secreted by a premalignant human colorectal adenoma cell line. 224 93

Two serine/threonine protein kinases were compared in C10, a clone from the nontumorigenic NAL IA cell line derived from normal mouse lung epithelium, and PCC4, a cell line derived from a mouse lung adenoma. C10 cells are contact inhibited, whereas PCC4 cells are not. Upon treatment with the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), the normally flattened C10 cells round up, while the normally bipolar, rounded PCC4 cells flatten out. Three proteins of 14,000, 20,000 and 116,000 molecular weight were phosphorylated in TPA-treated particulate fractions but not in untreated particulate fractions of PCC4 cells. In contrast, TPA caused a generalized increase in the phosphorylation of most membrane proteins in C10 cells. Cytosolic protein kinase C (PKC) specific activity was lower in PCC4 cells than in C10 cells, but particulate PKC activity was similar in the two cell lines. Both measurements of PKC activity and immunoblotting assays using anti-PKC antisera showed increased particulate PKC in TPA-treated C10 cells resulting from a quantitative translocation of PKC molecules from cytoplasm to plasma membrane. This PKC response to TPA was attenuated in PCC4 cells. While PCC4 particulate PKC activity was substantially increased after TPA treatment, PKC activity decreased only slightly in cytosolic fractions of TPA-treated PCC4 cells. Immunoblots of TPA-treated PCC4 cells showed a decline in cytosolic PKC content and increased particulate PKC concentration, but these changes were not of the same magnitude as the activity changes. This may represent an unmasking of latent PKC activity since particulate PKC activity in TPA-treated PCC4 cells was inhibited by staurosporine, a specific inhibitor of PKC when used at nanomolar concentrations. In addition, PCC4 cells had less mRNA coding for the R1 regulatory subunit of cyclic AMP (cAMP)-dependent protein kinase (PKA) than C10 cells, as determined by Northern blotting using an R1 alpha cDNA probe. Consistent with this result, photolabeling with 8-azido-[32P]cAMP, a photoaffinity analog of cAMP, revealed that R1 from PCC4 cells incorporated less analogue than R1 from C10 cells. PKA-specific activity also was lower in PCC4 cells than in C10 cells. Thus, deficiencies in protein kinases which mediate the effects of diacylglycerol and cAMP second messengers were observed in neoplastic lung cells. This may dampen the responsiveness of PCC4 cells to extracellular signals that regulate cell growth and cell-cell interactions.
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PMID:Altered function of protein kinase C and cyclic adenosine monophosphate-dependent protein kinase in a cell line derived from a mouse lung papillary tumor. 254 15

GH secretion and mRNA levels were measured in cultured human GH adenoma cells incubated in serum-free medium for up to 48 h. A human recombinant insulin-like growth factor I (IGF-I) analog, Thr-59-IGF-I (6.5 nM), inhibited basal GH secretion by up to 60% in tumor cell cultures. The 30-50% stimulation of GH secretion by GH-releasing hormone (GHRH) was prevented by simultaneous exposure of the cells to IGF-I (6.5 nM). Gel electrophoresis of total RNA derived from GH cell adenoma tissue, followed by transfer and hybridization with 32P-labeled human GH cDNA, revealed a distinct mRNA species of about 1.0 kilobases. Using cytoplasmic dot blot hybridization, IGF-I inhibited the levels of human GH mRNA sequences in these cells and also prevented the GHRH-induced stimulation of GH mRNA. A monoclonal antibody to the type I IGF-I receptor (alpha IR3) prevented the inhibitory effects of IGF-I on basal and GHRH-stimulated GH secretion. This antibody also prevented the IGF-I-induced suppression of GH mRNA sequences. PRL secretion in these cells was not altered by IGF-I. Furthermore, relative levels of beta-actin mRNA were unaltered by IGF-I. Thus, IGF-I suppresses basal and GHRH-stimulated GH secretion and GH mRNA levels in pituitary adenoma cells, indicating that IGF-I acts selectively on the somatotroph to directly regulate GH gene expression.
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PMID:Insulin-like growth factor I regulates growth hormone secretion and messenger ribonucleic acid levels in human pituitary tumor cells. 301 22

A pentapeptide with analgesic activity has been isolated from human lung squamous cell carcinoma and from three other types of propagated tumors of human lung small-cell carcinoma (SCC), adenoma (AD) and large-cell carcinoma (LCC) in nude mice. The amino acid sequence of the peptide has been revealed to be H-Thr-Ser-Lys-Tyr-Arg-OH, which is exactly the same as that of neo-kyotorphin, an analgesic peptide originally isolated from bovine brain [(1982) Life Sci. 31, 1733]. No neo-kyotorphin could be isolated from normal lung tissue using the same procedures as those used for carcinomas. The results suggest that the presence of neo-kyotorphin in the lung carcinoma may represent the ectopic expression of peptide hormone. Our findings constitute the first example of a human lung carcinoma producing analgesic peptide.
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PMID:Neo-kyotorphin, an analgesic peptide isolated from human lung carcinoma. 378 Sep 65

We have discovered two somatic mutations in the VI transmembrane domain of the thyrotropin receptor gene in thyroid hyperfunctioning adenomas. The mutated amino acid residues are phenylalanine 631 (to cysteine) and threonine 632 (to isoleucine). Cloning and expression of the mutated versions of the receptor in COS cells increased significantly the basal and the TSH-induced cAMP levels compared to the wild type receptor. Moreover, the expression of a reporter gene under the control of the cAMP-inducible promoter, was likewise constitutively activated in cells expressing the 631 and 632 TSH receptor mutants relative to the wild type. These data indicate that the VI transmembrane segment in the TSH receptor and presumably in the other G-protein coupled receptors is a critical domain for the activation of G-protein signalling and that the mutations described here may be the cause of the thyroid hyperfunctioning adenoma.
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PMID:Somatic mutations in the VI transmembrane segment of the thyrotropin receptor constitutively activate cAMP signalling in thyroid hyperfunctioning adenomas. 756 68

Constitutively activating mutations have recently been identified in the thyrotropin receptor (TSHR) of hyperfunctioning thyroid adenomas and familial hyperthyroidism. In the present study, we evaluated the frequency of constitutively activating TSHR mutations in a large series of autonomously functioning thyroid nodules (AFTNs) in Japan. Forty-five AFTNs (38 solitary hyperfunctioning thyroid adenomas and 7 toxic multinodular goiters) were analyzed. Genomic DNA was extracted from paraffin-embedded tissue sections, from which DNA fragments encoding the mutational hot spots of the receptor (the third cytoplasmic loop and the sixth transmembrane segment) were amplified by polymerase chain reaction. In the single-stranded conformation polymorphism (SSCP) analysis, only one hyperfunctioning adenoma (no. 21) displayed a migration abnormality. In sequence analysis, an unusual mutation of alternate three-base deletions at nucleotides 1953-1957 (AAA GAT ACC to AAG TCC), resulting in one amino acid deletion (Asp at 619) and one conservative amino acid substitution (Thr to Ser at 620), was identified in tumor DNA but not in leukocyte DNA of no. 21. Further, the normal sequence in these regions was confirmed in 10 randomly selected samples with normal migrating patterns in SSCP analysis. The functional property of the mutant with delta 619 and T620S (designated TSHR delta 619) was then evaluated with in vitro mutagenesis and transfection studies. Unexpectedly, however, there were no significant differences in TSH binding affinity, and basal and TSH-stimulated levels of cAMP and inositol 1,4,5-triphosphate between the TSHR delta 619 and the wt-TSHR. In conclusion, the incidence of the constitutively activating TSHR mutations in AFTNs appears to be low in Japan. The oncogenic potential of a novel somatic mutant TSHR delta 619 identified in a hyperfunctioning adenoma in this study is at present uncertain because of its intact function.
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PMID:Rarity of oncogenic mutations in the thyrotropin receptor of autonomously functioning thyroid nodules in Japan. 767 2

Germline point mutations in exons 10, 11, and 16 of the ret protooncogene have been identified as causative in multiple endocrine neoplasia type 2 and in familial medullary thyroid carcinoma (MTC). Somatic point mutations of the same gene, exclusively associated with codon 918 of exon 16, have also been reported in few cases of sporadic medullary thyroid carcinoma. We analyzed the blood and tumor DNA of 19 patients with sporadic MTC and 6 patients with primary parathyroid adenoma for point mutations at exons 10, 11, and 16 of the ret protooncogene by restriction analysis of the PCR-amplified product and by sequence analysis of exons 10 and 11. A Cys634-->Tyr mutation was found in both the tumoral and blood DNA of one patient, indicating that he was affected by an hereditary form of MTC, erroneously considered sporadic. In the other 18 patients with MTC, somatic point mutations of ret were found in 8 cases (44.4%). In 5 cases the mutation affected exon 16 (Met918-->Thr), and in 3 cases it affected exon 11 (Cys634-->Arg in 1 and Cys634-->Trp in 2); these 3 mutations were confirmed by sequence analysis. The remaining 10 patients had no mutation in exon 10 by either restriction analysis or sequence analysis. Clinical data showed that 75% of the patients whose tumor carried ret mutation had tumor recurrence and/or increased serum calcitonin concentrations during the postsurgical follow-up period as opposed to 10% of the patients without mutations (P < 0.02, by chi2 analysis). No ret mutation was found in the tumoral DNA from parathyroid adenomas. Our findings indicate that the somatic ret point mutation frequently found in sporadic MTC may affect not only exon 16 but also exon 11 and is associated with less favorable clinical outcome.
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PMID:Somatic mutations of the ret protooncogene in sporadic medullary thyroid carcinoma are not restricted to exon 16 and are associated with tumor recurrence. 863 77

Electrophysiological responses induced by human (h) growth hormone-releasing hormone (GHRH) were analyzed using the perforated whole cell clamp technique in human growth hormone (GH)-secreting adenoma cells. Application of hGHRH depolarized the membrane by increasing Na+ conductance. The reversal potential of the hGHRH-induced current was -20 to 0 mV. The channel was permeable to Na+, Li+ and K+ but not to TMA+. These properties were compatible with those of nonselective cation channels. Similar nonselective cation current was activated by 8-bromoadenosine 3',5'-cyclic monophosphate and forskolin, and the activation of the hGHRH-induced current was inhibited by protein kinase A (PKA) inhibitors, (R)-p-adenosine 3',5'-cyclic monophosphate and N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoleinsulfonamide, and PKA inhibitor peptide PKI-(5-24), indicating that hGHRH-induced current was activated by PKA. Cholera toxin pretreatment eliminated the hGHRH-induced current, suggesting that Gs is involved in the activation of this current. This current became irreversible when the cells were pretreated with okadaic acid, suggesting that the recovery of the hGHRH-induced current was mediated by a serine/threonine protein phosphatase. GHRH-induced GH secretion was inhibited in Na+-free medium, suggesting the importance of the nonselective cation current on hGHRH-induced GH secretion. In human GH-secreting nonadenoma cells, hGHRH increased Na+ conductance, as was the case in GH-secreting adenoma cells.
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PMID:GHRH activates a nonselective cation current in human GH-secreting adenoma cells. 876 91

Intestinal electroneutral NaCl absorption is mediated by parallel operation of Na(+)/H(+) and Cl(-)/HCO(3)(-) exchange in the enterocyte apical membrane. The ion transporters involved are Na(+)/H(+) exchanger 3 (NHE3) and the down regulated in adenoma (dra) gene product. cAMP-mediated inhibition of NHE3 requires the transporter to bind to the second PDZ (PSD95, disk large, ZO1) domain of the adapter protein NHE3 kinase A regulatory protein (E3KARP). Because the C-terminal four amino acids of dra are ETKF (glutamate-threonine-lysine-phenylalanine), resembling a PDZ interaction motif, we hypothesized that dra may also bind to one of the PDZ domains of E3KARP. In vitro the ETKF motif of dra binds to the second PDZ domain of E3KARP, the affinity being comparable to that of the known ligand CFTR. The C-terminal phenylalanine, which is an unconventional residue in PDZ interaction motifs, can only be substituted by the classical residue leucine, but not by other hydrophobic residues (valine, isoleucine). Immunofluorescence colocalizes dra, NHE3, and E3KARP in the apical compartment of human proximal colon. We suggest a model in which both NHE3 and dra bind to the second PDZ domain of E3KARP and that linking of the transporters occurs through dimerization of E3KARP. In such a model, the first PDZ domain would remain available for instance for signal transduction proteins.
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PMID:The down regulated in adenoma (dra) gene product binds to the second PDZ domain of the NHE3 kinase A regulatory protein (E3KARP), potentially linking intestinal Cl-/HCO3- exchange to Na+/H+ exchange. 1236 22

Polo-like kinase 1 (PLK1) is one of the serine threonine kinases that contributes to cell mitosis and is regarded as a marker of cellular proliferation. However, its protein expression in human carcinoma has not been studied in depth. We investigated PLK1 expression in various thyroid neoplasms in order to elucidate its physiological significance in thyroid carcinoma. Normal follicular cells only occasionally expressed PLK1. In follicular tumours and anaplastic carcinoma, PLK1 overexpression was not a common event and only 5.9% of follicular adenoma, 7.1% of follicular carcinoma, and 11.8% of anaplastic carcinoma overexpressed this protein. However, 43.7% of papillary carcinoma overexpressed PLK1. Polo-like kinase 1 overexpression was more frequently observed in smaller papillary carcinoma lesions, and 62.5% of microcarcinoma (ranging from 4 mm to 1.0 cm) and even 66.7% of incidental carcinoma (less than 4 mm) overexpressed it, whereas this phenomenon could only be seen in 20.0% of lesions larger than 4.0 cm. Furthermore, PLK1 overexpression was not related to cell-proliferating activity evaluated by Ki-67 labelling index, but it was inversely linked to UICC stage, extrathyroidal invasion, and the presence of poorly differentiated lesion as proposed by Sakamoto et al. These findings strongly suggest that, unlike other carcinomas previously studied, PLK1 does not act as a cell cycle regulator but plays a constitutive role in papillary carcinoma especially in the early phase, and may contribute to the malignant transformation of this carcinoma.
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PMID:Polo-like kinase 1 overexpression is an early event in the progression of papillary carcinoma. 1473 86


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