Structure and expression of c-myc and c-fos proto-oncogenes in thyroid carcinomas

Terrier, Philippe; Sheng, Zong‐Mei; Schlumberger, Martin; Tubiana, M; Caillou, Bernard; Travagli, Jean-Paul; Fragu, P.; Parmentier, C; Riou, G

doi:10.1038/bjc.1988.6

Cited by 80 publications

(42 citation statements)

References 31 publications

(39 reference statements)

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“…Frozen tissues were ground in liquid nitrogen and nucleic acids extracted by the guanidinium-thiocyanate method. DNA and RNA were fractionated by centrifugation in a CsCl gradient (Maniatis et al, 1982;Terrier et al, 1988). Nucleic acids were also prepared from EJ human cancer cell line.…”

Section: Methodsmentioning

confidence: 99%

Analysis of the c-Ha-ras-1 gene for deletion, mutation, amplification and expression in lymph node metastases of human head and neck carcinomas

Sheng

Barrois²,

Klijanienko³

et al. 1990

Br J Cancer

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Summary The c-Ha-ras gene was analysed by Southern blot hybridisation in 67 specimens of lymph node metastases and in 25 specimens of primary tumours obtained from 85 untreated patients with head and neck squamous cell carcinoma. The loss of one c-Ha-ras allele was observed in 10/46 (22%) tumours from heterozygous patients for this locus. Different genes, located as the c-Ha-ras gene on the short arm of chromosome 11, were also found to be deleted suggesting that the deletion of other genes could play a role in aggressiveness of head and neck carcinomas. Using polymerase chain reaction, mutation at codon 12 was detected in only 2/54 (3.8%) tumours but no mutation involving codon 61 was found. Neither gene amplification nor gene rearrangement could be observed. Total RNA was prepared from 79 of these tumour specimens and analysed by Northern and slot blot hybridisation. A 1.2 kb c-Ha-ras transcript band was detected in all the RNA preparations. Relatively high c-Ha-ras transcript levels were found in 18% of lymph node metastases and in 21% of primary tumours, indicating no significant differences between these cancers. Moreover, the c-Ha-ras mRNA levels were not significantly greater in the primary tumours than in the normal mucosae in 10/12 cases for which both tissues were analysed. These data indicate that c-Ha-ras gene does not seem to be strongly involved in head and neck carcinomas at that advanced stage of the disease, as this was previously reported for earlier clinical stages.It is now well established that genetic alterations are implicated in the biological deregulation of cancer cells and that the cellular oncogenes are involved in the cancer process (Bishop, 1987;Merkel & McGuire, 1988;Nordenskjold & Cavenee, 1988). Among those cellular oncogenes, the ras genes were thought to play an important role and many studies were initiated to detect alterations and aberrant expression of these genes. Somatic mutations, resulting in the substitution of a single base at particular positions in the gene locus were found to be responsible for oncogenic activity by transfection assay, in about 15% of cancers (Barbacid, 1988). Recently, using more sensitive methods, high rates of mutation affecting the c-Ki-ras gene were detected in DNA from pancreas and colon carcinomas (Bos et al., 1987;Forrester et al., 1987;Almoguera et al., 1988;Bos, 1989). In colon tissues the c-Ki-ras mutations were even found in the precancerous lesions which were assumed to progress in invasive carcinomas. Mutations of the ras gene were also found in thyroid adenomas and carcinomas (Lemoine et al., 1988;Suarez et al., 1988). C-Ha-ras mutation at codon 12 was shown to be associated with cervical cancers of poor prognosis . A c-Ha-ras restriction fragment length polymorphism (RFLP) (Capon et al., 1983) (Barbacid, 1988). On the contrary, studies on the expression of ras genes indicated that high levels of ras-specific messenger RNA and ras p21 protein were associated with tumour progression in human cancers of different origins (Viola et al...

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Section: Methodsmentioning

confidence: 99%

Analysis of the c-Ha-ras-1 gene for deletion, mutation, amplification and expression in lymph node metastases of human head and neck carcinomas

Sheng

Barrois²,

Klijanienko³

et al. 1990

Br J Cancer

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“…Na tireóide normal, há controvérsia quanto à expressão destes genes; Aasland et al 27 encontraram-na elevada inclusive com altos níveis do mRDA do c-myc e do c-fós, contrariamente a outros autores 32,33 que relatam baixos níveis destes mRDA em amostras de tecido tireoidiano normal. Embora a expressão do c-myc e de c-fós esteja elevada em alguns carcinomas tireoidianos, principalmente nos anaplásicos, nenhuma amplificação ou rearranjos destes proto oncogenes foi encontrada e a maioria dos estudos publicados não mostrou importância deles na tumorigênese dos tumores epiteliais da tireóide 27,32,34 .…”

Section: Receptores Associados a Proteínas Nuclearesunclassified

“…Embora a expressão do c-myc e de c-fós esteja elevada em alguns carcinomas tireoidianos, principalmente nos anaplásicos, nenhuma amplificação ou rearranjos destes proto oncogenes foi encontrada e a maioria dos estudos publicados não mostrou importância deles na tumorigênese dos tumores epiteliais da tireóide 27,32,34 . O c-myc parece ter participação importante na proliferação celular, como ocorre na Doença de Graves 33 .…”

Section: Receptores Associados a Proteínas Nuclearesunclassified

A biologia molecular no prognóstico do carcinoma da tireóide

Rodrigues

2003

Rev. Col. Bras. Cir.

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INTRODUÇÃOO carcinoma da tireóide, como outros tumores malignos do organismo humano, origina-se de uma única célula, alterada por lesões dos genes que controlam a proliferação celular. O comportamento biológico do câncer tireoidiano é muito variado e embora, em sua maioria, apresente comprometimento clinicamente indolente, em alguns casos assume características agressivas, com invasão local e metástases à distância, que podem resultar no óbito do paciente.Excluindo-se os carcinomas anaplásicos, invariavelmente fatais com qualquer tipo de tratamento, os diferenciados e os medulares admitem terapêuticas mais ou menos agressivas, de acordo com o comportamento biológico do tumor. Por isso, nas duas últimas déca-das, diversos autores vêm procurando definir os fatores de risco que apresentam valor prognóstico na evolução destes tumores, especialmente na variedade diferenciada, tornando possível dividi-los em dois grupos: tumor de alto e de baixo risco, com condutas terapêuti-cas diferentes em cada grupo [1][2][3][4][5] . Os fatores de risco avaliados baseiam-se em dados clínicos e anatomopatológicos que em análises multivariadas, mostraram-se independentemente responsáveis pelo prognóstico da doença. Entretanto, mesmo em pacientes considerados de baixo risco nestas classificações, alguns tumores podem eventualmente desenvolver comportamento mais agressivo. O estudo da expressão de oncogenes, de antioncogenes bem como de genes implicados na adesão celular e na disseminação tumoral, tem procurado aprimorar a avaliação prognóstica dos tumores tireoidianos a nível molecular 6 . ONCOGENES E ANTIONCOGENES NO CÂNCER DE TIREÓIDEUm melhor conhecimento da biologia molecular possibilitou o entendimento de alterações celulares que levam à formação e disseminação dos tumores. Diversos fatores estimulam a proliferação e a diferenciação celulares (genes estimuladores); outros são inibidores desta proliferação (genes supressores). Do inter-relacionamento adequado destes fatores resulta o funcionamento normal de órgãos e tecidos. As proteínas normais codificadas pelos genes estimuladores atuam na membrana celular, no citoplasma e no núcleo. Agem como fatores de crescimento, como receptores destes fatores, como proteínas envolvidas na transmissão de sinais dentro das células (mensageiros secundários) e como proteínas reguladoras nucleares. Na tireóide, os principais fatores estimulantes da proliferação celular e/ou de suas funções são o hormônio tireotrófico da hipófise (TSH), o fator de crescimento epidérmico (EGF), o fator de crescimento transformador ∝ (TGF∝) e o fator de crescimento semelhantes à insulina (IGF). Outros fatores menos importantes mas com ação semelhante, são o fator de crescimento fibroblasto básico (BFGF), a gonadotropina coriônica humana (hCG), o hormônio de crescimento (GH) e o fator de crescimento do hepatócito (HGF) entre outros. Entre os genes supressores estão o p53 e o fator de crescimento transformador β (TGFβ).Os fatores estimulantes codificam receptores específicos na célula que, ativados, modificam e t...

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“…160,164,165, The abundance of c-myc transcripts may thus be predictive of the outcome of thyroid malignancy. 160,164,165 Where examined, there is a tendency for TSH receptor transcript abundance to correlate negatively with those for c-myc. 164,165 …”

Section: C-myc In Thyroid Cancermentioning

confidence: 99%

“…138,[160][161][162] Immuno-histochemical studies and those of c-myc mRNA indicated an increased expression in thyroid tumor tissue. 111,112,160,162,163 Apparently, the less differentiated a tumor, the greater the abundance of c-myc transcripts. 160,164,165, The abundance of c-myc transcripts may thus be predictive of the outcome of thyroid malignancy.…”

Section: C-myc In Thyroid Cancermentioning

confidence: 99%

Towards Understanding the Molecular Basis of Thyroid Cancer

Farid

1995

Annals of Saudi Medicine

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Structure and expression of c-myc and c-fos proto-oncogenes in thyroid carcinomas

Cited by 80 publications

References 31 publications

Analysis of the c-Ha-ras-1 gene for deletion, mutation, amplification and expression in lymph node metastases of human head and neck carcinomas

Analysis of the c-Ha-ras-1 gene for deletion, mutation, amplification and expression in lymph node metastases of human head and neck carcinomas

A biologia molecular no prognóstico do carcinoma da tireóide

Towards Understanding the Molecular Basis of Thyroid Cancer

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