Jakowlew S B, Mathias A, Chung P, Moody T W
National Cancer Institute, Biomarkers and Prevention Research Branch, Rockville, Maryland 20850, USA.
Cell Growth Differ. 1995 Apr;6(4):465-76.
Specific cDNA probes for transforming growth factor beta s (TGF-beta s) 1, 2, and 3 and TGF-beta types I, II, and III receptors were used to study expression of the mRNAs of the different TGF-beta ligand and TGF-beta receptor isoforms in cultured non-small cell lung cancer (NSCLC) cells and small cell lung cancer (SCLC) cells. Expression of TGF-beta 1 mRNA was detected in both cell types using Northern blot hybridization, with the level of expression of this mRNA being higher in several NSCLC cell lines. In addition, expression of TGF-beta 2 and TGF-beta 3 mRNAs was also detected in NSCLC and SCLC cells but at levels that were lower than that of TGF-beta 1 mRNA. Besides expression of a 3.4-kilobase (kb) TGF-beta 3 transcript, a smaller 2.8-kb TGF-beta 3 transcript was detected in some NSCLC and SCLC cells. TGF-beta 1 and TGF-beta 2 proteins were detected in the conditioned media of NSCLC and SCLC cells, with the levels being higher in several NSCLC cells than in SCLC cells. Expression of TGF-beta types I and II receptor mRNAs was also detected in most NSCLC and SCLC cells, with expression of a 5.5-kb type I receptor mRNA being higher than that of a 5.5-kb type II receptor mRNA in both cell types. In contrast, a 6-kb TGF-beta type III receptor mRNA was detected in only some NSCLC cells and could not be detected in the SCLC cells examined. Also, there was an inverse relationship between the level of expression of the 5.5-kb TGF-beta type I receptor mRNA and that of the 6-kb TGF-beta type III receptor mRNA. Addition of TGF-beta 1 and TGF-beta 2 proteins resulted in an increase in the mRNAs for TGF-beta s 1 and 2 and an increase in the amount of TGF-beta 1 protein in some NSCLC cells, indicating that these cells are responsive to TGF-beta and its effects. At the same time, a differential change in expression of the 2.8- and 3.4-kb TGF-beta 3 transcripts was detected in some lung cancer cells following the addition of TGF-beta 1 and TGF-beta 2. Also, addition of TGF-beta 1 to NSCLC cells inhibited colony formation of some of these cells in soft agarose in a dose-dependent manner.(ABSTRACT TRUNCATED AT 400 WORDS)
使用针对转化生长因子β（TGF-β）1、2和3以及TGF-β I、II和III型受体的特异性cDNA探针，研究不同TGF-β配体和TGF-β受体亚型的mRNA在培养的非小细胞肺癌（NSCLC）细胞和小细胞肺癌（SCLC）细胞中的表达情况。通过Northern印迹杂交在两种细胞类型中均检测到TGF-β1 mRNA的表达，在几种NSCLC细胞系中该mRNA的表达水平更高。此外，在NSCLC和SCLC细胞中也检测到了TGF-β2和TGF-β3 mRNA的表达，但表达水平低于TGF-β1 mRNA。除了3.4千碱基（kb）的TGF-β3转录本表达外，在一些NSCLC和SCLC细胞中还检测到了较小的2.8 kb的TGF-β3转录本。在NSCLC和SCLC细胞的条件培养基中检测到了TGF-β1和TGF-β2蛋白，几种NSCLC细胞中的水平高于SCLC细胞。在大多数NSCLC和SCLC细胞中也检测到了TGF-β I和II型受体mRNA的表达，在两种细胞类型中，5.5 kb的I型受体mRNA的表达高于5.5 kb的II型受体mRNA。相反，仅在一些NSCLC细胞中检测到6 kb的TGF-β III型受体mRNA，在所检测的SCLC细胞中未检测到。此外，5.5 kb的TGF-β I型受体mRNA的表达水平与6 kb的TGF-β III型受体mRNA的表达水平呈负相关。添加TGF-β1和TGF-β2蛋白导致一些NSCLC细胞中TGF-β 1和2的mRNA增加以及TGF-β1蛋白量增加，表明这些细胞对TGF-β及其作用有反应。同时，在添加TGF-β1和TGF-β2后，在一些肺癌细胞中检测到2.8 kb和3.4 kb的TGF-β3转录本表达的差异变化。此外，向NSCLC细胞中添加TGF-β1以剂量依赖的方式抑制了其中一些细胞在软琼脂糖中的集落形成。（摘要截断于400字）
