Re-expression of ABI3-binding protein suppresses thyroid tumor growth by promoting senescence and inhibiting invasion
Re-expression of ABI3-binding protein suppresses thyroid tumor growth by promoting senescence and inhibiting invasion
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DOI：
10.1677/erc-08-0079
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发表时间：
2008-09-01
影响因子：
3.9
通讯作者：
Cerutti, Janete M.
中科院分区：
文献类型：
--
作者：
Latini, Flavia R. M.;Hemerly, Jefferson P.;Cerutti, Janete M.
ABI基因家族成员3结合蛋白（ABI 3BP）表达的缺失可能在癌症的发病机制中起作用。以前的报道已经表明在肺癌中的表达缺失和在诱导细胞衰老中的假定作用。我们在这里显示，ABI 3BP表达显着降低，在所有类型的大多数恶性甲状腺肿瘤。为了更好地理解ABI 3BP的作用，我们通过在两种甲状腺癌细胞系中重新表达ABI 3BP来创建模型。甲状腺细胞中ABI 3BP的重新表达导致裸鼠中转化活性、细胞生长、细胞活力、迁移、侵袭和肿瘤生长的降低。ABI 3BP再表达似乎通过p21途径触发细胞衰老。此外，ABI 3BP诱导异染色质1结合蛋白γ阳性衰老相关（SA）异染色质灶的形成和SA β-半乳糖苷酶的积累。细胞生长、侵袭和其他对体外ABI 3BP再表达的影响的减少的组合有助于解释我们在裸鼠中观察到的肿瘤生长的大幅减少。总之，我们的数据提供的证据表明，ABI 3BP表达的损失可能在甲状腺肿瘤的发生中发挥作用。ABI 3BP或其通路的激活可能代表某些癌症的靶向治疗的可能基础。内分泌相关癌症（2008）15 787-799
Loss of ABI gene family member 3-binding protein (ABI3BP) expression may be functionally involved in the pathogenesis of cancer. Previous reports have indicated a loss of expression in lung cancer and a presumed role in inducing cellular senescence. We show here that ABI3BP expression is significantly decreased in most malignant thyroid tumors of all types. To better understand ABI3BPs role, we created a model by re-expressing ABI3BP in two thyroid cancer cell lines. Re-expression of ABI3BP in thyroid cells resulted in a decrease in transforming activity, cell growth, cell viability, migration, invasion, and tumor growth in nude mice. ABI3BP re-expression appears to trigger cellular senescence through the p21 pathway. Additionally, ABI3BP induced formation of heterochromatin 1-binding protein gamma-positive senescence-associated (SA) heterochromatin foci and accumulation of SA beta-galactosidase. The combination of a decrease in cell growth, invasion, and other effects upon ABI3BP re-expression in vitro helps to explain the large reduction in tumor growth that we observed in nude mice. Together, our data provide evidence that the loss of ABI3BP expression could play a functional role in thyroid tumorigenesis. Activation of ABI3BP or its pathway may represent a possible basis for targeted therapy of certain cancers. Endocrine-Related Cancer (2008) 15 787-799