RESUMO
An altered protein expression of Ca(2+)-dependent protein kinase C (PKC) isoforms and a point mutation in the PKC alpha cDNA (position 908 of the nucleotide sequence, position 294 of the amino acid sequence, substitution of an aspartic acid by a glycine) have been previously described in a subpopulation of human pituitary tumors. In this work, we screened 16 thyroid tissue samples (four follicular adenomas, five colloid adenomas, three papillary carcinomas, one follicular carcinoma and three normal tissues adjacent to the tumors) for the presence of the PKC alpha point mutation and for PKC alpha, beta 1, beta 2, epsilon and delta protein expression. Screening for the presence of the PKC alpha mutant was performed by a subcloning technic. The polymerase chain reaction products were generated using reverse-transcribed cDNAs, subcloned and sequenced (10 clones were routinely sequenced). The PKC alpha point mutation at position 908 of the cDNA sequence was found in four out of the nine adenomas and in the follicular carcinoma. It was neither detected in the papillary carcinomas nor in the adjacent normal tissues (one was the adjacent normal tissue of the follicular carcinoma; in this sample, genomic DNA and cDNA were used to look for the presence of the mutant), demonstrating the somatic nature of this mutant. Western blot analysis of PKC isoforms showed that the expression of all isoforms was higher in the thyroid neoplasms as compared with their adjacent normal tissue (n = 3). It was also higher in the samples containing the PKC mutant (two follicular adenomas, two colloid adenomas and the follicular carcinoma) as compared with the tumors where it was not detected (three papillary carcinomas and five adenomas). Samples could be ordered according to their increasing PKC expression as follows: normal adjacent tissue < follicular adenomas without PKC alpha mutant < or = papillary carcinoma < follicular adenomas with PKC mutant < follicular carcinoma with PKC mutant. In conclusion, the discovery of the PKC alpha mutant in thyroid neoplasms demonstrates that this mutant is not particular to human pituitary tumors where it was originally detected. It is a somatic mutation and its presence is concomitant with high levels of all of the PKC isoforms analysed. The presence of the PKC mutant in thyroid neoplasms raises the question of its importance in thyroid tumorigenesis.
Assuntos
Isoenzimas/genética , Mutação Puntual , Proteína Quinase C/genética , Neoplasias da Glândula Tireoide/enzimologia , Neoplasias da Glândula Tireoide/genética , Adenocarcinoma Folicular/enzimologia , Adenocarcinoma Folicular/genética , Adenocarcinoma Mucinoso/enzimologia , Adenocarcinoma Mucinoso/genética , Adenoma/enzimologia , Adenoma/genética , Sequência de Bases , Carcinoma/enzimologia , Carcinoma/genética , Carcinoma Papilar/enzimologia , Carcinoma Papilar/genética , Clonagem Molecular , Primers do DNA , DNA Complementar , DNA de Neoplasias/análise , DNA de Neoplasias/genética , Humanos , Dados de Sequência Molecular , Reação em Cadeia da PolimeraseAssuntos
Tecido Adiposo , Composição Corporal , Hormônios Esteroides Gonadais/sangue , Síndrome do Ovário Policístico/fisiopatologia , Acantose Nigricans/complicações , Adolescente , Adulto , Amenorreia/genética , Amenorreia/metabolismo , Amenorreia/fisiopatologia , Feminino , Humanos , Hipotálamo/fisiopatologia , Insulina/sangue , Obesidade/complicações , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/metabolismo , Estudos ProspectivosRESUMO
Among 6,035 people living in 3 villages from the area of La Kara (Togo), 984 randomized subjects were investigated to evaluate goiter prevalence and related etiologic factors. Creatinine and thiocyanates (SCN-) were measured in urine, thyroid hormones and TSH in plasma. Iodine was evaluated in urine, water, salt, soil, millet and sorgho. The amount of cassava was evaluated in food. Mean goiter prevalence was 32%, reaching to 45.9% in one village; urinary iodine remained in a low range (27.2 +/- 2.18 micrograms/g creatinine in adults, 34.3 +/- 6.7 in children--m +/- SEM) independently of the presence of endemic goiter. Urinary SCN- was increased. Low iodine values were found in food, salt, soil and water which contained few mineral elements except flour which was increased in the samples collected in one of the 3 villages. Cretinism was absent, T4, T3, TSH remained in a normal range. This study confirms a high prevalence of endemic goiter in the area of La Kara with iodine deficiency, leading to an urgent iodine supplementation.