Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

A monoclonal antibody (TCM-9) specific for human thyroid cancer but not for Graves' disease, adenoma or normal thyroid tissue was shown to recognize a 300 K protein but not to bind to native or mature human thyroglobulin (Tg). In this study, we investigated further the antigen recognized by TCM-9. When purified Tg was treated with periodate, dithiothreitol (DTT) and sodium dodecyl sulfate (SDS), immunoblotting of treated Tg with TCM-9 revealed an apparent enhancement of the staining only with DTT-treated Tg. Furthermore, the DTT-treated Tg was shown to bind dose-dependently to plates coated with TCM-9. We performed SDS-PAGE and immunoblot analyses on the immune complex obtained from a homogenate of thyroid cancer tissue which was preincubated with an excess of anti-Tg monoclonal antibody. When the protein was autoradiographed with [125I]TCM-9, a definite band was observed. The results indicate that TCM-9 is likely to be directed against a masked epitope of thyroglobulin which can be exposed after treatment with a reducing agent.
Mol Cell Endocrinol 1993 Jun
PMID:A thyroid cancer specific monoclonal antibody which recognizes cryptic epitope(s) of human thyroglobulin. 768 5

A thyroid carcinoma cell line, BHT-101, has been established in vitro from a metastatic lymph node deposit in a female patient with a non-hormone producing anaplastic, partly thyroglobulin- and thyroxine (T4)-positive papillary thyroid cancer. The cell population is heterogeneous, containing epithelial-like and fibroblast-like cells, and has a doubling time of 24 h. The cell line is polyploid with hypertetraploid predominance and the karyotype showed trisomies, tetrasomies, pentasomies as well as many marker chromosomes. The majority of the cells are negative or weakly positive for thyroglobulin and thyroxine and estrogen and progesterone receptors are present in the cells. BHT-101 cells produce tumours when injected into immunosuppressed CBA/Ca mice. The cells are sensitive to adriamycin, methotrexate and tamoxifen but not to methimazole (Favistan). The epithelial-like clone 1 and the fibroblast-like clone 3, isolated from the parental line, differed in drug sensitivity. This new cell line is suitable for studying the biology of thyroid carcinoma and for parallel in vivo and in vitro studies of drug activity against thyroid cancer.
Virchows Arch B Cell Pathol Incl Mol Pathol 1993
PMID:Establishment, characterization and drug sensitivity of a new anaplastic thyroid carcinoma cell line (BHT-101). 809 64

p16INK4a (MTS1) is an important negative regulator of mammalian cell proliferation, acting via inhibition of CDK4/cyclin D-dependent phosphorylation of pRb to prevent progression through the G1 phase of the cell cycle. Loss of p16 activity by either gene deletion, mutation or transcriptional inactivation has now been found in a wide range of human cancers of both epithelial and mesenchymal origin, at a frequency rivalling that of p53 mutation. As a first step towards investigating its possible role as a tumour suppressor gene in thyroid tumorigenesis, we have carried out a Southern blot analysis of the p16 gene locus in a series of cell lines derived from differentiated human thyroid cancers. Homozygous deletion of the entire p16 coding sequence was observed in two of three follicular and two of four papillary cancer cell lines, but not in normal tissue or normal cells immortalised by SV40 T antigen. Given the co-existence of p16 abnormalities in primary tumours and cell lines observed in other tumour types, this high frequency of deletion suggests that p16 is a key tumour suppressor gene in the genesis of differentiated thyroid cancer.
Mol Cell Endocrinol 1996 Jan 15
PMID:High frequency deletion of the tumour suppressor gene P16INK4a (MTS1) in human thyroid cancer cell lines. 882 72

Cowden disease, also known as multiple hamartoma syndrome, is an autosomal dominant cancer syndrome with a high risk of breast and thyroid cancer. The gene involved has been localized to chromosome 10q22-23. Recently, the tumour suppressor gene PTEN/MMAC1, encoding a putative protein tyrosine or dual-specificity phosphatase, was cloned from that region and three mutations were detected in patients with Cowden disease. We confirmed that the PTEN/MMAC1 gene is indeed the gene for Cowden disease by a refined localization of the gene to the interval between D10S1761 and D10S541, which contains the PTEN/MMAC1 gene and, by mutation analysis in eight unrelated familial and 11 sporadic patients with Cowden disease. Eight different mutations were detected in various regions of the PTEN/MMAC1 gene. One mutation was detected twice. All detected changes in the gene can be predicted to have a very deleterious effect on the putative protein. Five of the nine patients have a mutation in exon 5 coding for the putative active site and flanking amino acids. Evaluation of the clinical data of the patients in which a mutation could be detected gives no clear indications for a correlation between the genotype and phenotype. In 10 patients no mutation could be detected so far. In support of the linkage data, no evidence has emerged from the phenotype of these patients suggestive for genetic heterogeneity.
Hum Mol Genet 1997 Aug
PMID:Germline mutations in the PTEN/MMAC1 gene in patients with Cowden disease. 925 88

Extracellular nucleotides like ATP that activate the Ca2+ -phosphatidylinositol (PI) signalling pathway have been suggested to participate in the regulation of normal human thyroid function. We examined, whether P2y-purinergic receptors are expressed on human thyroid cancer cells and whether post-receptor Ca2+ signalling is altered by malignant transformation. Extracellular ATP caused a biphasic increase in cytosolic free Ca2+ ([Ca2+]i) in normal human thyrocytes and in human follicular (FTC) and papillary (PTC) thyroid carcinoma cells. In FTC and PTC cell lines the dose-response curves for ATP-induced changes in [Ca2+]i were shifted to the right when compared with normal thyrocytes, whereas in undifferentiated thyroid carcinoma (UTC) cells even high concentrations of ATP (500 microM) failed to stimulate a rise in [Ca2+]i. By contrast, ATP stimulated inositol 1,4,5-trisphosphate (IP3) formation and capacitative Ca2+ entry was operational as judged by thapsigargin in normal thyrocytes and all thyroid cancer cells. Thus, P2y-purinergic receptors are expressed on thyroid tumor cells independent of degree of differentiation. In UTC cells, however, impairment in the Ca2+ -phosphatidylinositol (PI) signalling cascade occurs distal to the formation of IP3 and proximal to the activation of capacitative Ca2+ entry. Disturbed ATP-induced Ca2+ -signalling and alterations in the Ca2+ -PI signalling cascade may contribute to decreased expression or loss of specific thyroid functions in thyroid cancer cells.
Mol Cell Endocrinol 1997 Sep 30
PMID:Impairment of ATP-induced Ca2+ -signalling in human thyroid cancer cells. 935 70

Previously, we and others have found that the prognosis of patients with well differentiated thyroid cancer is related to patient age and gender. In this study, we examined estrogen and glucocorticoid receptors in thyroid cancers and adjacent non-neoplastic thyroid tissues from 31 Chinese patients. Our results indicate that the level of estrogen and glucocorticoid receptors in thyroid cancer tissues was similar to that in non-neoplastic thyroid tissues. Significant higher estrogen and glucocorticoid receptor levels were found in thyroid cancers from men than women. There was no difference in estrogen receptor levels from thyroid cancer in women less than or older than 45. However, the level of glucocorticoid receptor in thyroid cancer from women less than 45 years old was significantly higher than that of women older than 45. Estrogen or glucocorticoid receptor levels did not correlate with tumor invasiveness. The pathobiological role of glucocorticoid receptors in thyroid cancer is not known but may be involved in changes in circadian rhythm of thyroid tumors.
Int J Mol Med 1998 Aug
PMID:Estrogen receptors and glucocorticoid receptors in human well-differentiated thyroid cancer. 985 94

The validity of molecular studies using DNA and RNA extracted from decades-old formalin-fixed and paraffin-embedded tissue blocks has been demonstrated. The quality and usability of DNA and RNA from archival tissues are modified by various factors, such as the fixative, the fixation time, and the postmortem time. However, in contrast to DNA, there are no comprehensive studies quantitatively addressing the feasibility of RNA from old (more than 10 years) archival samples. This study examined the integrity of RNA extracted from 738 autopsy liver and 63 autopsy thyroid cancer tissue blocks procured during a span of nearly four decades, beginning in 1952 and ending in 1989, from the atomic bomb survivors. The integrity of RNA was assessed by amplification of c-BCR messenger RNA (mRNA) between two sequential exons with an intervening intron by reverse-transcription polymerase chain reaction (RT-PCR). The integrity of RNA was influenced by the age of the samples and the postmortem time, but not by the formalin-fixation period. It was possible to amplify more than 60% of the samples. Using these RNAs, the HCV genome in liver cancers and the H4-RET gene in thyroid cancers were detectable. This study illustrates the possibility of molecular studies using RNA from routinely prepared paraffin blocks stored for long periods and provides the statistics and critical factors to consider in assessing the feasibility of such contemplated studies.
Diagn Mol Pathol 1998 Aug
PMID:RNA from decades-old archival tissue blocks for retrospective studies. 991 30

Our earlier reports indicated that the changes of age-adjusted incidence rates (AAIRs) of any 2 tumors in time and space, as investigated by the sequential regression analysis, showed a good fitness to the equilibrium model under the control of the law of mass action. The purpose of this study is to investigate the problem of whether or not the changes of AAIRs of individual tumors in time and space show a similar fitness to the equilibrium model of the law of mass action. The cancer risk data set of: a) 20 neoplasias in scope; b) 6 cancer registration areas in space; and c) 5 sequential investigations from early 1960's to mid 1980's in time, were subjected to the sequential regression analysis - a modification of the least square method. Results obtained are as follows: a) out of 20 tumors tested, all tumors other than 5 tumor types showed a good fitness (P<0.05) to the equilibrium model of the law of mass action in their risk changes in space. The 5 tumor types that failed to fit to the equilibrium model were male gall-bladder cancer, male breast cancer, male thyroid cancer, female liver cancer and female laryngeal cancer. They were all classified as the members of low-risk gender in the cancer family with sex discrimination of cancer risk. b) All tumors other than male thyroid cancer of Birmingham-England showed a good fitness to the equilibrium model of the law of mass action in their risk changes in time. c) It is argued that the good fitness to the equilibrium model of the law of mass action and the poor fitness to the equilibrium model can be taken each as indication of the predominant expression of oncogene activation and the emergence of intervention of tumor suppressor gene inactivation to the full expression of oncogene activation in the mathematical structure of the cancer risk data set. The significance of the above findings as the supporting evidence of the steroid criminal hypothesis of carcinogenesis as well as the pertinence of the least square method to the mathematical analysis of cancer risk are discussed in the light of historical development of science from early 19th century to late 20th century.
Int J Mol Med 1999 Apr
PMID:Statistical analysis of the age-adjusted incidence rates of human neoplasias: changes in time and space from early 1960's to mid 1980's with special reference to the steroid criminal hypothesis of carcinogenesis. 1008 20

The present study is an extension of our recent study in which we attempted statistical analysis of the data assembly of age-adjusted incidence rates (AAIRs) of a tumor without topological data manipulation for each of 20 individual tumors in scope, for each of 6 cancer registration areas in space, and for a period of early 1960's to mid 1980's in time. This time, a data assembly of log AAIR changes in time and space first passed through the process of topological data manipulation, and then underwent the sequential regression analysis so that we could assess the fitness of log AAIR changes either in space or in time to the equilibrium model of the law of mass action from the viewpoint of the interaction between oncogene activation and tumor suppressor gene inactivation. For the sake of comparison, the fitness of the cancer risk data to the equilibrium model was assessed in the framework of 3 sets of coordinates: a) the original (x org, y org) coordinates in which most of the log AAIR data assemblies in their data variations were classified as the oncogene activation type in the field of centripetal force (r seq=-1.000). b) The rect (X rect, Y rect) coordinates in which the log AAIR data assemblies were very often classified as the tumor suppressor gene inactivation type in the field of centrifugal force (r seq=+1.000). c) The para (X para, Y para) coordinates in which the log AAIR data assemblies were mostly classified as the intermediate type as regards the fitness to the equilibrium model. The rect-coordinates and the para-coordinates, 2 variants of angular rotation of the original coordinates, were so designed as to allow their X-axes to run each at a right angle and parallel to the regression line of the original pair data block. The results obtained were as follows: a) poor fitness of the log AAIR changes in space to the equilibrium model in the rect-coordinates was found in male breast cancer, male thyroid cancer, female esophageal cancer, female laryngeal cancer and female lung cancer. The summation of the present study and the last study from our laboratory led to the conclusion that the members of low-risk gender in the tumor family with sex discrimination of cancer risk were inclined to show either failed expression of oncogene activation or failed expression of tumor suppressor gene inactivation or both. b) There was a subtle difference of the fitness of log AAIR data to the equilibrium model between the log AAIR changes in time and those in space in that the log AAIR changes in time within the framework of the rect-coordinates, which usually represented the field of centrifugal force or site of tumor suppressor gene inactivation expression, showed an increase in the number of oncogene activation type data sets as compared with the log AAIR changes in space. c) Upon further insight into the AAIR changes in time, consistent association of prominent cancer risk increase in time with the transition of tumor suppressor gene inactivation expression (r seq=+1.000) from the rect-coordinates to the para-coordinates was detected in skin cancer of both sexes, testicular tumor, liver cancer of both sexes and thyroid cancer of both sexes, all of which were related to the prevalence of environmental hormones as regards the recent boost of their cancer risks in the Western countries. In summary, the log AAIR, a cancer risk parameter, in its changes in time and space was found to provide useful information in assessing the interaction between the oncogene-tumor suppressor gene complex and the hormonal milieu of the host in the genesis of both environmental hormone-dependent and -independent human neoplasias. The significance of our statistical maneuver (the sequential regression analysis) is discussed in the light of the development of mathematics in early 19th century.
Int J Mol Med 1999 Aug
PMID:Topological transition of the parametric expression site of tumor suppressor inactivation as a marker evidence of environmental hormone-oriented cancer risk increase. 1040 82


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