Coordinate suppression of Sdpr and Fhl1 expression in tumors of the breast, kidney, and prostate
Coordinate suppression of Sdpr and Fhl1 expression in tumors of the breast, kidney, and prostate
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DOI：
10.1111/j.1349-7006.2008.00816.x
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发表时间：
2008-07-01
期刊：
影响因子：
5.7
通讯作者：
Goldberg, Gary S.
中科院分区：
文献类型：
--
作者：
Li, Xun;Jia, Zhenyu;Goldberg, Gary S.
Src酪氨酸激酶与粘着斑适配蛋白Cas（Crk相关底物）结合以抑制潜在肿瘤抑制基因的表达。例如，Src利用Cas抑制仅LIM蛋白Fhl 1（四个半LIM结构域1）的表达，以促进非锚定肿瘤细胞生长和迁移。在这里，我们报告的Fhl 1基因的启动子区域甲基化更多的Src转化细胞比非转化细胞。此外，全局表达分析表明，Fhl 1诱导表达的血清剥夺反应因子（Sdpr）在Src转化细胞。此外，Fhl 1和Sdpr在约87%和40%的从非转化乳腺获得的样品、100%的从非转化肾脏获得的样品和超过60%的从非转化前列腺获得的样品中表达。相比之下，在大约40%和7%的乳腺癌匹配样本中检测到Fhl 1和Sdpr，在不到11%的肾癌匹配样本中检测到Fhl 1和Sdpr，在不到22%的前列腺癌匹配样本中检测到Fhl 1和Sdpr。这些数据表明，Fhl 1和Sdpr在乳腺癌（P < 0.02和P < 0.001）、肾癌（P < 0.01）和前列腺癌（P < 0.05）中的表达显著降低。此外，虽然Src可以激活丝裂原活化蛋白激酶（MAPK），以促进肿瘤细胞的生长，我们的数据表明，Src并不依赖于MAPK活性抑制Fhl 1和Sdpr在转化细胞的表达。因此，Src诱导Fhl 1基因的启动子区域的甲基化; Src抑制Fhl 1和Sdpr的表达，而不依赖于丝裂原活化蛋白激酶（MAPK）活性; Fhl 1诱导Src转化细胞中Sdpr的表达;并且Fhl 1和Sdpr的表达在乳腺、肾脏和前列腺肿瘤中被抑制。
The Src tyrosine kinase associates with the focal adhesion adaptor protein Cas (Crk-associated substrate) to suppress the expression of potential tumor suppressor genes. For example, Src utilizes Cas to suppress the expression of the LIM-only protein Fhl1 (four and a half LIM domains 1), in order to promote non-anchored tumor-cell growth and migration. Here, we report that the promoter region of the Fhl1 gene was methylated more in Src-transformed cells than non-transformed cells. In addition, global expression analysis indicates that Fhl1 induced expression of serum deprivation response factor (Sdpr) in Src-transformed cells. Moreover, Fhl1 and Sdpr was expressed in approximately 87% and 40% of samples obtained from non-transformed breast, 100% of samples obtained from non-transformed kidney, and over 60% of samples obtained from non-transformed prostate. In contrast, Fhl1 and Sdpr was detected in approximately 40% and 7% of matched samples from mammary carcinoma, less than 11% of matched samples from kidney carcinoma, and in less than 22% of matched samples from prostate carcinoma. These data indicate that Fhl1 and Sdpr expression was significantly reduced in tumors of the breast (P < 0.02 and P < 0.001), kidney (P < 0.01), and prostate (P < 0.05). In addition, although Src can activate mitogen-activated protein kinase (MAPK) to promote tumor-cell growth, our data indicate that Src did not rely on MAPK activity to suppress the expression of Fhl1 and Sdpr in transformed cells. Thus, Src induced methylation of the promoter region of the Fhl1 gene; Src suppressed Fhl1 and Sdpr expression independent of mitogen-activated protein kinase (MAPK) activity; Fhl1 induced the expression of Sdpr in Src-transformed cells; and Fhl1 and Sdpr expression was suppressed in tumors of the breast, kidney, and prostate.