Inactivation of the transforming growth factor beta type II receptor in human small cell lung cancer cell lines.
Inactivation of the transforming growth factor beta type II receptor in human small cell lung cancer cell lines.
复制标题
人类小细胞肺癌细胞系中转化生长因子II型受体的失活。
DOI：
10.1038/sj.bjc.6690161
复制
发表时间：
1999-03
影响因子：
8.8
通讯作者：
Poulsen, HS
中科院分区：
文献类型：
--
作者：
Hougaard, S;Norgaard, P;Abrahamsen, N;Moses, HL;Spang-Thomsen, M;Poulsen, HS
关键词：
转化生长因子β（TGF-β）通过与两种类型的受体（I型和II型受体）结合，对许多细胞类型发挥生长抑制作用。由于缺乏II型受体（RII）而对TGF-β的抗性已经在包括小细胞肺癌（SCLC）的一些癌症类型中描述。本研究的目的是检查SCLC细胞系中缺乏RII表达的原因。北方印迹分析显示，21个细胞系中有16个细胞系的RII RNA表达很弱。为了研究RII转录物的缺失是否是由于突变引起的，我们筛选了poly-A道的突变，但未检测到突变。对RII基因突变的额外筛选揭示了在一个不表达RII的细胞系中GG到TT碱基取代。该突变产生终止密码子，导致预测的219个氨基酸的截短RII的合成。以前在RII中没有观察到的突变的性质与暴露于苯并[a]-芘（香烟烟雾的一种成分）有关。由于RII已被定位到染色体3p22，并且附近的基因座在SCLC中通常是高甲基化的，因此检查了RII表达的缺乏是否是由于高甲基化。RII启动子的Southern印迹分析未显示改变的甲基化模式。RII基因的限制性内切酶的模式被改变，在两个小细胞肺癌细胞系，Sma 1消化时。然而，5-氮-2 ′-脱氧胞苷处理不能诱导RII mRNA的表达。我们的研究结果表明，在小细胞肺癌缺乏RII mRNA是不常见的，由于突变和失活的RII转录不是由于超甲基化的RII启动子或基因。因此，这些数据表明，在SCLC细胞系的大多数情况下，尽管不存在RII表达，但RII基因和启动子是完整的。然而，发现的突变的性质可能表明它是由吸烟引起的。© 1999癌症研究运动
Transforming growth factor β (TGF-β) exerts a growth inhibitory effect on many cell types through binding to two types of receptors, the type I and II receptors. Resistance to TGF-β due to lack of type II receptor (RII) has been described in some cancer types including small cell lung cancer (SCLC). The purpose of this study was to examine the cause of absent RII expression in SCLC cell lines. Northern blot analysis showed that RII RNA expression was very weak in 16 of 21 cell lines. To investigate if the absence of RII transcript was due to mutations, we screened the poly-A tract for mutations, but no mutations were detected. Additional screening for mutations of the RII gene revealed a GG to TT base substitution in one cell line, which did not express RII. This mutation generates a stop codon resulting in predicted synthesis of a truncated RII of 219 amino acids. The nature of the mutation, which has not previously been observed in RII, has been linked to exposure to benzo[a]-pyrene, a component of cigarette smoke. Since RII has been mapped to chromosome 3p22 and nearby loci are often hypermethylated in SCLC, it was examined whether the lack of RII expression was due to hypermethylation. Southern blot analysis of the RII promoter did not show altered methylation patterns. The restriction endonuclease pattern of the RII gene was altered in two SCLC cell lines when digested with Sma 1. However, treatment with 5-aza-2′-deoxycytidine did not induce expression of RII mRNA. Our results indicate that in SCLC lack of RII mRNA is not commonly due to mutations and inactivation of RII transcription was not due to hypermethylation of the RII promoter or gene. Thus, these data show that in most cases of the SCLC cell lines, the RII gene and promoter is intact in spite of absent RII expression. However, the nature of the mutation found could suggest that it was caused by cigarette smoking. © 1999 Cancer Research Campaign
登录
查看更多内容
DOI：
10.1073/pnas.89.5.1929
发表时间：
1992-03-01
影响因子：
11.1
作者：
MAKOS, M;NELKIN, BD;BAYLIN, SB
通讯作者：
BAYLIN, SB
影响因子：
64.5
作者：
LIN, HY;WANG, XF;LODISH, HF
通讯作者：
LODISH, HF
影响因子：
2.5
作者：
MOSES, HL
通讯作者：
MOSES, HL
DOI：
10.1073/pnas.91.19.8772
发表时间：
1994-09-13
影响因子：
11.1
作者：
PARK, KC;KIM, SJ;SPORN, MB
通讯作者：
SPORN, MB
影响因子：
8.8
作者：
Damstrup, L;Rygaard, K;Spang-Thomsen, M;Skovgaard Poulsen, H
通讯作者：
Skovgaard Poulsen, H