Alterations of thyroid hormone receptor alpha gene: frequency and association with Nm23 protein expression and metastasis in gastric cancer.
Alterations of thyroid hormone receptor alpha gene: frequency and association with Nm23 protein expression and metastasis in gastric cancer.
复制标题
DOI：
10.1016/s0304-3835(01)00722-4
复制
发表时间：
2002-01
期刊：
影响因子：
9.7
通讯作者：
Chia-Siu Wang;Kwang-Huei Lin;Y. Hsu
中科院分区：
文献类型：
--
作者：
Chia-Siu Wang;Kwang-Huei Lin;Y. Hsu
甲状腺激素受体基因（c-erbA或TR）与肿瘤抑制基因有关。我们研究了两种TR基因亚型（TRα和TRβ）在人胃癌中是否发生改变，以及这种改变在肿瘤转移中的作用。作为初步调查（n=18），用限制性内切酶（EcoRI、BamHI或HindIII）酶切后，用全长TRα或TRβ cDNA探针进行Southern blot分析。调查显示，最常见的改变是在TRα基因上，丢失了两个HindIII片段（7.1和10.1 kb）。随后的研究通过将患者数量增加到42例来关注这种TRα改变。39例患者中有19例（49%）出现TRα改变，结果具有信息性。TRα的改变与远处（血行）转移的发生（P=0.0084）和Nm23蛋白的高表达（P=0.020）相关。这些发现提示，TRα可能参与了胃癌的发生，TRα与nm23基因的相互作用可能参与了胃癌的血行转移。
Thyroid hormone receptor genes (c-erbA, or TR) have been implicated as tumor suppressor genes. We investigated whether two subtypes of TR genes (TRα and TRβ) are altered in human gastric cancer, as well as the role of such alterations in tumor metastasis. As a preliminary survey (n=18), Southern blot analysis was conducted with full-length TRα or TRβ cDNA probes, after digestion with restriction enzyme (EcoRI, BamHI, or HindIII). The survey showed the most frequent alteration was in TRα gene by a loss of two HindIII fragments (7.1 and 10.1 kb). Subsequent study focused at this TRα alteration by increasing patient number up to a total of 42. TRα alteration was noted in 19 (49%) of the 39 patients with informative results. The TRα alteration was associated with the development of distant (hematogenous) metastasis (P=0.0084) and high expression level of Nm23 protein (P=0.020). These findings suggest that TRα might be involved in tumorigenesis, and that interactions between the TRα and nm23 genes might take part in hematogenous metastasis of gastric cancer.