Expression profiling of genes regulated by TGF-beta: differential regulation in normal and tumour cells.
Expression profiling of genes regulated by TGF-beta: differential regulation in normal and tumour cells.
复制标题
DOI：
10.1186/1471-2164-8-98
复制
发表时间：
2007-04-11
期刊：
影响因子：
4.4
通讯作者：
Kondaiah P
中科院分区：
文献类型：
--
作者：
Ranganathan P;Agrawal A;Bhushan R;Chavalmane AK;Kalathur RK;Takahashi T;Kondaiah P
TGF-β是参与包括癌症在内的各种疾病过程的关键细胞因子之一。TGF-β抑制正常上皮细胞的生长并促进细胞凋亡，相反，通过促进肿瘤血管生成、免疫逃逸和转移来充当促肿瘤细胞因子。目前尚不清楚TGF-β对正常细胞和肿瘤细胞的各种作用是否是由于不同的基因调控。因此，我们研究了正常细胞和癌细胞中TGF-β对基因表达的调节。使用人类19 K cDNA微阵列，我们发现，1757个基因是专门由TGF-β在A549细胞中的733个基因专门在HPL 1D细胞中调节相反。此外，267个基因在两种细胞系中共同调控。一些基因的半定量和实时qRT-PCR分析与微阵列数据一致。为了鉴定影响TGF-β介导的基因调控的信号通路，我们使用了p38 MAP激酶、ERK激酶、JNK激酶和整联蛋白信号通路的特异性抑制剂。这些数据表明，大多数选定的基因的调节依赖于这些途径中的至少一种，并且这种依赖性是细胞类型特异性的。有趣的是，一种整合素途径抑制剂，RGD肽，显著影响A549细胞中血小板反应蛋白1的TGF-β调节。这些数据表明，在正常和转化细胞中TGF-β介导的基因调控方面存在重大差异，非经典TGF-β途径在TGF-β对许多基因的调控中发挥重要作用。
TGF-beta is one of the key cytokines implicated in various disease processes including cancer. TGF-beta inhibits growth and promotes apoptosis in normal epithelial cells and in contrast, acts as a pro-tumour cytokine by promoting tumour angiogenesis, immune-escape and metastasis. It is not clear if various actions of TGF-beta on normal and tumour cells are due to differential gene regulations. Hence we studied the regulation of gene expression by TGF-beta in normal and cancer cells. Using human 19 K cDNA microarrays, we show that 1757 genes are exclusively regulated by TGF-beta in A549 cells in contrast to 733 genes exclusively regulated in HPL1D cells. In addition, 267 genes are commonly regulated in both the cell-lines. Semi-quantitative and real-time qRT-PCR analysis of some genes agrees with the microarray data. In order to identify the signalling pathways that influence TGF-beta mediated gene regulation, we used specific inhibitors of p38 MAP kinase, ERK kinase, JNK kinase and integrin signalling pathways. The data suggest that regulation of majority of the selected genes is dependent on at least one of these pathways and this dependence is cell-type specific. Interestingly, an integrin pathway inhibitor, RGD peptide, significantly affected TGF-beta regulation of Thrombospondin 1 in A549 cells. These data suggest major differences with respect to TGF-beta mediated gene regulation in normal and transformed cells and significant role of non-canonical TGF-beta pathways in the regulation of many genes by TGF-beta.
登录
查看更多内容
影响因子：
4.7
作者：
Kloth, JN;Fleuren, GJ;Gorter, A
通讯作者：
Gorter, A
影响因子：
6.5
作者：
Asano, Yoshihide;Ihn, Hironobu;Tamaki, Kunihiko
通讯作者：
Tamaki, Kunihiko
影响因子：
11.4
作者：
LUND, LR;ROMER, J;DANO, K
通讯作者：
DANO, K
影响因子：
11.2
作者：
Ao, Mingfang;Williams, Karin;Hayward, Simon W.
通讯作者：
Hayward, Simon W.
影响因子：
5.6
作者：
DANIELPOUR, D;DART, LL;SPORN, MB
通讯作者：
SPORN, MB