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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report immunohistochemical evidence for the overexpression of protein kinase C in various proliferative diseases of human thyroid. Immunohistochemical characterization of various surgically removed thyroid tissues, viz., cancer tissues: papillary carcinoma and follicular carcinoma; adenoma tissues: tubular, trabecular and colloid adenomas; adenomatous goiter; and normal thyroid was done using the monospecific monoclonal antibodies MC-1a, MC-2a and MC-3a, each of which is specific for types I, II and III isozymes of protein kinase C, respectively. For protein kinase C type II, a remarkable difference in staining intensity was noted between the cancerous and normal tissues. The cytoplasm of papillary and follicular carcinoma cells stained more intensely than that of normal thyroid cells. In the benign tumor and adenomatous goiter tissues, stronger staining was noted in the papilliform-proliferating portion and cubic epithelial cells. In the normal thyroid tissues, epithelial cells of greater height were more strongly stained than simple squamous epithelial cells. These results indicated that protein kinase C type II isozyme is expressed in larger amounts in cancerous and proliferative tissues of the human thyroid.
Cell Mol Biol 1991
PMID:Immunohistochemical evidence for the overexpression of protein kinase C in proliferative diseases of human thyroid. 180 90

Highly purified thyroglobulin mRNA was isolated from human nodal euthyroid goiter. Full length cDNA was synthesized from 33S RNA by using reverse transcriptase in the presence of human placenta ribonuclease inhibitor. DNA complementary to human Tg mRNA was used in liquid hybridization experiments to determine the quantity of Tg mRNA. The amount of Tg mRNA in euthyroid nodal and congenital goiter was reduced. Tg specific mRNA was absent in thyroid cancer cells.
Mol Biol (Mosk)
PMID:[Thyroglobulin gene expression in human thyroid cells in various types of thyroid pathology]. 258 2

It has been proposed from in vivo studies that thyroid angiogenesis during thyroid enlargement may be due to paracrine mitogenic factors released by epithelial thyroid cells. To study this paracrine growth regulating communication between thyroid cells and endothelial cells in vitro, culture medium from isolated porcine thyroid follicles was investigated for a growth promoting effect on porcine aortal endothelial cells. Serum-free conditioned medium (CM) from thyroid follicles in suspension culture contains a dose-related mitogenic activity which stimulates endothelial cell growth up to 197%. Stimulation of the thyroid follicles with TSH (1 mU/ml) significantly reduced the mitogenic activity for endothelial cells in CM to 131%. Thyroid hormones had no influence on mitogenic activity in CM. When follicles were treated with iodide (20 microM) during CM production, no proliferation of endothelial cells was observed by this CM. In contrast, CM from epidermal growth factor-treated thyroid follicles significantly enhanced the mitogenic activity for endothelial cells up to 235%. The mitogenic activity was precipitable by saturated ammonium sulfate, showed high affinity to heparin by chromatography on heparin-sepharose, and was abolished after treatment of CM with trypsin. On gel electrophoresis the heparin-binding fraction showed a double band with a mol wt of 15 and 15.5 k. These data show a paracrine mitogenic activity on endothelial cells released by thyroid follicles which is regulated by TSH, epidermal growth factor, and iodide in parallel with the direct effect of these substances on thyroid cell growth. The data suggest that the mitogenic factor is a polypeptide, which belongs to the heparin-binding growth factors.
Mol Endocrinol 1989 May
PMID:Release of an endothelial cell growth factor from cultured porcine thyroid follicles. 266 51

The morphological and functional changes during involution of hyperplastic goitre have been investigated in the adult male rat. Male wistar rats received an iodine-deficient diet for 6 months and during the last 2 months received propylthiouracil (PTU, 0.15%). By the end of this treatment (day 0), a hyperplastic goitre was obtained. A normal iodine supply was then given and PTU withdrawn. During the first 8 days of iodine refeeding, the plasma thyrotropin (TSH) remained at a high level (ten times the control value), whereas the thyroid iodide content was low on day 0, markedly increased on day 1 and decreased on day 4. Plasma T3 and T4 levels remained unchanged for 4 days and only increased on day 8. The total thyroid protein concentration was low on day 0 and then increased rapidly on day 8 (by 34%). The volume density of colloid remained low and unchanged until day 8, when it started to increase. However, the thyroid epithelial cell volume and the volume density of capillaries were raised on day 0, decreased rapidly in the next 8 days and more slowly later on. The total number of thyroid epithelial cells was considerably raised in the hyperplastic gland. It did not vary until day 16, when it decreased slowly, reaching a plateau on day 45 above the control value. The present data show that involution of hyperplastic goitre in the rat is due essentially to a decrease in thyroid epithelial cell volume and to a reduction of the increased number of capillary blood vessels present. The decrease in the number of epithelial cells is only 16.5%, suggesting that the death of thyroid epithelial cells contributes little. Half the process of involution, which occurs from days 0 to 8, is controlled by the thyroid iodide concentration rather than TSH, indicating the involvement of a thyroid autoregulatory mechanism. It must be emphasized, however, that the discontinuous pattern of epithelial cell number during involution may indicate that some cells with larger nuclei and more rapid turnover disappear more quickly after iodine refeeding.
Virchows Arch B Cell Pathol Incl Mol Pathol 1987
PMID:Involution of hyperplastic goitre in the adult male rat. Tissue compartment process with early iodide effect: a stereological and biochemical study. 288 35

A functioning rat thyroid cell line (FRTL5) was used to study interactions of thyrotropin (TSH) and various cytokines on expression of class I and II major histocompatibility complex (MHC) antigens and on growth stimulation. Only gamma-interferon (gamma-IFN) affected MHC antigen expression, i.e., to enhance class I, that was constitutive, and to induce class II. A concomitant, but probably not directly related, effect of gamma-IFN was to diminish growth stimulation, as effected by TSH and other activators of adenylate cyclase and measured by DNA increase and enhanced incorporation of [3H]thymidine into DNA. Stimulation of growth by tetradecanoylphorbol ester was also decreased by gamma-IFN. These effects of gamma-IFN were mimicked to some degree by tumor necrosis factor but there was major synergism between the two cytokines. Enhanced accumulation of cAMP by TSH and other agents was not diminished in these experiments. Flow cytometry analysis showed that inhibition of growth stimulation involved blocking of the passage of cells from the G0/1 phase to the S phase. The data may have relevance to goiter size in autoimmune thyroid disease.
Mol Cell Endocrinol 1988 Aug
PMID:Effects of gamma-interferon and tumor necrosis factor alpha on thyroid cells: induction of class II antigen and inhibition of growth stimulation. 314 28

Sustained elevation of serum thyrotropin (TSH) induces an initial proliferation of rat thyroid follicular cells, leading to goitre formation followed by a 'plateau phase' in which the growth response to TSH is lost. To investigate this growth desensitisation mechanism, we have compared the sensitivity to growth factors of normal and 'plateau phase' rat thyroid epithelium in primary follicle cultures. Insulin at supraphysiological concentrations stimulates growth (DNA synthesis) in both cell types. TSH at a concentration found in 'plateau phase' animals (0.1 mU/ml) is maximally growth stimulatory for normal, but not significantly stimulatory for 'plateau' epithelium. At much higher concentrations however (greater than or equal to mU/ml) an equal response is obtained from both. We conclude that the growth desensitising mechanism is intrinsic to the follicular cell, is at least partly specific to TSH, and is effective only over the range of TSH concentrations found in vivo.
Mol Cell Endocrinol 1987 May
PMID:In vitro demonstration of a TSH-specific growth desensitising mechanism in rat thyroid epithelium. 329 48

A goat strain with congenital goiter was studied as a model for human thyroid disoders. These goats were deficient in thyroglobulin (Tg), the precursor protein of the thyroid hormones T3 and T4. RNA coding for Tg (Tg-RNA) was detected in reduced amounts in the goiters and was almost absent from the membranes, where Tg is normally synthesized. This paper describes the preparation and characterization of a goat Tg cDNA plasmid and its use in the study of thyroglobulin gene expression in the goiter. We found that the goiter Tg-RNA is polyadenylated and has the same size as normal 33S goat TG mRNA. Thus, there are no major defects in the mRNA processing. However, in contrast to normal Tg mRNA, the goiter Tg-RNA was not translated into immunoprecipitable Tg subunits when injected into Xenopus oocytes. We conclude therefore that the goiter Tg-RNA has one or more alterations causing a lack of proper translation and/or a decreased cytoplasmic stability.
J Mol Appl Genet 1981
PMID:Nonfunctional thyroglobulin messenger RNA in goats with hereditary congenital goiter. 612 53

Patterns of cAMP-dependent protein kinases and cAMP-independent histone and casein kinases of hyperplastic rat thyroid glands and of human nodular non-toxic goitres have been analysed in two subcellular compartments, cytosol and particulate fraction. In hyperplastic rat glands the different compartmentalization of the two cAMP-dependent isoenzymes was preserved and the pattern of cAMP-independent protein kinases was not changed qualitatively, but the activities of the three classes of protein kinases were enhanced to different degrees: the highest increase was observed for the cAMP-dependent enzymes and the lowest for the cAMP-independent casein kinases. Analysis of individual peaks of cAMP-dependent kinases showed selective stimulation of the cytosolic Type II form and independent control of the Type I activity in the two subcellular compartments. Among cAMP-independent protein kinases only two histone kinase peaks were selectively enhanced; other kinase entities were changed to a lesser degree. During the involution of hyperplastic glands, a transient but differential enhancement of nearly all kinases was noted at first, which was followed later by a strong decrease, more or less rapid, of almost all kinase activities. In the regressed glands, neither the thyroid weight nor the pattern of different kinase entities corresponded to those of control, untreated glands, indicating that some of the protein kinase alterations in hyperplastic tissues are partly irreversible. In spite of great similarities, human and rat goitre tissues are not identical. The most important difference was the loss of compartmentalization of the cAMP-dependent isoenzymes in human tissue. The different ratios of the light and heavy peaks of cytosolic cAMP-independent histone kinases was the second characteristic which distinguished human and rat glands.
Mol Cell Endocrinol 1983 Dec
PMID:Protein kinase patterns in hyperplastic rat thyroids and in human non-toxic nodular goitres. 631 84

Porcine thyroid follicle cells, cultured in suspension, were employed to investigate the effects of immunoglobulin preparations from patients with colloid goitre, Graves' disease or Hashimoto's thyroiditis on thyroid growth in vitro. Epidermal growth factor (EGF, 19 ng/ml) was used as a reference for maximum growth stimulation and produced a 9-fold increase in [3H]thymidine incorporation. Immunoglobulins (1000 micrograms/ml) were found to increase [3H]thymidine incorporation compared to control: from 10 normal individuals 32 +/- 4% (mean +/- SEM, % of EGF response), from 10 patients with colloid goitre 26 +/- 4% (not significantly different from normal), from 10 patients with Graves' disease 19 +/- 3% (P less than 0.05) and from 15 patients with Hashimoto's thyroiditis 11 +/- 2% (P less than 0.001). No patient immunoglobulin preparation showed activity greater than that of normal individuals. The lower growth stimulatory activity in Graves' disease and Hashimoto's thyroiditis remained after heat inactivation of serum and is thought to reflect surface binding of thyroid autoantibodies.
Mol Cell Endocrinol 1984 Mar
PMID:Influence of thyroid autoantibodies on thyroid cellular growth in vitro. 660 95

Clonality studies have suggested that neoplasms are monoclonal and hyperplasias are polyclonal. To investigate this question in thyroid, we analyzed the clonality of 26 morphologically characterized hyperplastic nodules from 19 patients with sporadic goiters. For comparison we studied six thyroid carcinomas. We used the highly informative M27 beta probe that maps to the X-chromosome DXS255 locus (X cen-p11.22). Material was obtained from 52 nodules; tissue from nine nodules was rejected because of contamination with normal elements, five patients (eight nodules) were homozygous at Pst I sites in nonnodular thyroid tissue, and three nodules were excluded for technical reasons. Methylation patterns after Hpa II digestion confirmed polyclonality in all nontumorous thyroids of informative patients. Seven hyperplastic nodules were polyclonal, and 18 were monoclonal; one showed loss of heterozygosity. One nodule exhibited aberrant methylation. Multiple nodules were obtained from four patients; in three, all were monoclonal with activation of the same allele. Three papillary carcinomas were monoclonal; two exhibited aberrant methylation. One follicular carcinoma showed loss of heterozygosity. Our data indicate that morphologically indistinguishable hyperplastic thyroid nodules may be monoclonal or polyclonal. These findings suggest that variable molecular mechanisms are involved in the pathogenesis of nodules in sporadic goiter. Future studies will need to explore the biological significance of nodules of variable clonal origin.
Diagn Mol Pathol 1995 Jun
PMID:Clonality of thyroid nodules in sporadic goiter. 755 Dec 91


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