High expression of the sister-chromatid separation regulator and proto-oncogene hSecurin occurs in a subset of myeloid leukaemias but is not implicated in the pathogenesis of aneuploidy

Abstract

High expression of the sister-chromatid separation regulator and proto-oncogene hSecurin occurs in a subset of myeloid leukaemias but is not implicated in the pathogenesis of aneuploidy Aneuploidy is considered to play an important role in the pathogenesis of malignancies. We were interested whether abnormalities of the sister-chromatid separation regulator and proto-oncogene hSecurin occurred in myeloid leukaemias, and whether such abnormalities correlated with aneuploidy. The expression of hSecurin was assessed by real-time quantitative PCR in samples from patients with acute myeloid leukaemia (AML, n ¼ 70), chronic myeloid leukaemia (CML) in chronic phase (CP, n ¼ 20) or blast phase (BP, n ¼ 12), and granulocytes as well as mononuclear cells (MNCs) from healthy donors (n ¼ 21). Median hSecurin expression in AML with normal karyotypes was not significantly different from AML showing aneuploidy, CML BP or cells from healthy donors. However, hSecurin expression in CML CP was significantly increased compared to AML with normal karyotypes (1.82-fold; Po0.001), CML BP (3.18-fold; Po0.001), MNCs (3.17-fold; Po0.001) and granulocytes (2.69 fold; Po0.001) from healthy donors. Mutations in the coding region of hSecurin were not detected. These results do not support a major role of hSecurin in the development of aneuploidy in myeloid leukaemias. However, high expression of hSecurin may be of pathogenetic relevance in a subset of patients with regard to its potential to stimulate angiogenesis and to interact with the DNA-damage response pathway.

Overexpression of pituitary tumor transforming gene 1 in HCC is associated with angiogenesis and poor prognosis†

“…10,11 A more recent report, however, demonstrated that high expression of PTTG1 did not contribute to the development of DNA aneuploidy in myeloid leukemias. 24 Univariate and multivariate analyses showed that only PTTG1 expression was significantly associated with both disease-free and overall survival rates. This result indicates that PTTG1 overexpression might help to identify the HCC patients with poor prognoses and that its expression could be a potentially novel prognostic marker of HCC.…”

Genes hSecurina e VEGF e células endoteliais circulantes como marcadores de angiogênese em portadores de leucemia mielóide crônica

“…Recentemente alguns autores demonstraram associação entre hiperangiogênese e expressão anômala da proteína securina humana (hsecurina) que é codificada pelo gene idêntico ao transformador do tumor pituitário (PTTG) (Auner et al, 2004). Estes estudos não tiveram como objetivo verificar a associação entre expressão de hsecurina e angiogênese na LMC.…”

“…Estes estudos não tiveram como objetivo verificar a associação entre expressão de hsecurina e angiogênese na LMC. Os autores sugerem que a hiperexpressão de hsecurina pode estar relacionada à elevação da taxa de proliferação celular desencadeada pelo gene quimérico BCR-ABL e que a hsecurina pode estimular a síntese de fator básico de crescimento de fibroblastos, potencializando a angiogênese na LMC (Auner et al, 2004). Além disso, o impacto do aumento de expressão do VEGF sérico no curso da LMC ainda é desconhecido (Verstovsek et al, 2002 (Geary, 2000).…”

“…Se intacta, a securina suporta o acúmulo nuclear da separase, inibindo sua atividade proteolítica. (Auner et al, 2004;Gil-Barnabé et al, 2006). …”

Estudo da expressão do gene hSecurina e quantificação do índice de DNA em portadores assintomáticos do vírus linfotrópico T humano tipo 1 e pacientes com leucemia/linfoma de células T do adulto

“…Ao ser ubiquitada, a securina torna-se sensível ao APC/C, liberando, então, a separase (Figura 8) que passa a clivar as subunidades das proteínas Scc1, Mcd1, Rad21. Conseqüentemente desfaz a coesão entre os cromossomos e libera a célula em direção à anáfase na qual as cromátides irmãs migram para eixos opostos da célula16 . Desta forma, a degradação da securina assegura a transição normal da metáfase para a anáfase e a separação adequada dos cromossomos durante a mitose10 .…”