新型转录因子BCL-9调控甲状腺癌骨转移及溶骨破坏的机制研究

Thyroid carcinoma is the most common cancer of the endocrine system.Thyroid carcinoma is the bone-seeking tumor,with high rate of bone metastasis.The 10-year survival rate drops to 13%-21% when bone metastasis happens.we found a transcriptional coregulators called BCL-9 in the thyroid carcinoma rising remarkably.Animal experiments also demonstrates that BCL-9 is highly correlated to bone metastasis of thyroid carcinoma,as well as bone destruction.Further studies reveal that BCL-9 is a possible independant transcription factor regulated the relevant gene expression of proliferation,metastasis,osteolysis of thyroid carcinoma.So far no study has been reported between BCL-9 and bone metastasis.This project aims at testing the expression of BCL-9 in the clinical specimens,detecting the relation to the bone metastasis,further studying the regulatory mechanism of BCL-9 towards the genes of proliferation,metastasis,as well as osteolysis of thyroid carcinoma such as PTHrP,galactin-3,RANKL,etc.we want to study the key function of BCL-9-mediated thyroid carcinoma-bone microenvironment,in order to provide new theoretical basis and drug target for the treatment of bone metastasis from thyroid carcinoma.

甲状腺癌是内分泌系统最常见的恶性肿瘤，属亲骨性肿瘤，易发生骨转移，甲状腺癌发生骨转移后，十年生存率降低至13%-21%。在甲状腺癌中我们发现一种转录协同因子BCL-9在骨转移灶中的含量显著升高，动物实验证实BCL-9同甲状腺癌骨转移的发生和骨质破坏高度相关，进一步的研究显示，BCL-9可能作为一个独立的转录因子，调控与甲状腺癌增殖、转移、骨溶解相关的基因表达。且BCL-9与甲状腺癌骨转移的关系目前尚未有报道。本项目拟通过检测临床标本中BCL-9的表达，明确其与甲状腺癌骨转移的关系；进一步研究BCL-9对PTHrP、Galectin-3、survivin等与甲状腺癌增殖、转移、骨溶解等相关基因表达的调控机制；揭示BCL-9介导甲状腺癌-骨微环境之间关键作用，为甲状腺癌骨转移治疗提供新的理论基础及药物靶点。

甲状腺癌是内分泌系统最常见的恶性肿瘤，属亲骨性肿瘤，易发生骨转移，甲状腺癌发生骨转移后，十年生存率降低至13%-21%。在甲状腺癌中我们发现一种转录协同因子BCL-9在骨转移灶中的含量显著升高，动物实验证实BCL-9同甲状腺癌骨转移的发生和骨质破坏高度相关，进一步的研究显示，BCL-9可能作为一个独立的转录因子，调控与甲状腺癌增殖、转移、骨溶解相关的基因表达。且BCL-9与甲状腺癌骨转移的关系目前尚未有报道。本项目通过检测临床标本中BCL-9的表达，明确其与甲状腺癌骨转移的关系；进一步研究BCL-9对PTHrP、Galectin-3、survivin等与甲状腺癌增殖、转移、骨溶解等相关基因表达的调控机制；揭示BCL-9介导甲状腺癌-骨微环境之间关键作用，为甲状腺癌骨转移治疗提供新的理论基础及药物靶点。