Ye Q, Wei Y, Fischer R, Borner C, Berchtold M W
Institute of Veterinary Biochemistry, University of Zürich, Switzerland.
Biochim Biophys Acta. 1997 Oct 30;1359(1):89-96. doi: 10.1016/s0167-4889(97)00086-4.
Molecular mechanisms leading to elevated calmodulin (CaM) expression in cancer have not yet been discovered. We have quantitated the levels of transcripts derived from all three CaM genes in a variety of the same origin rat fibroblasts transformed with oncogenes in combination with gene for protein kinase C using Northern blot analysis with three CaM gene specific cDNA probes. Five species of CaM mRNA were detected in all these cells. Surprisingly many of the investigated cell lines exhibited a decreased content of all CaM mRNAs as compared to control cells with CaMI and CaMII transcripts showing the most pronounced alterations. In contrast, CaM protein levels were increased in all these cell lines as determined by a radioimmunoassay. These results suggest that oncogenic up-regulation of CaM synthesis takes place posttranscriptionally. Several CaM binding proteins were found at different concentrations in the studied cell lines depending on the oncogenes used for transformation. However, CaM overexpression does not seem to affect the overall levels of CaM binding proteins.
导致癌症中钙调蛋白(CaM)表达升高的分子机制尚未被发现。我们使用三种CaM基因特异性cDNA探针,通过Northern印迹分析,对多种由癌基因与蛋白激酶C基因共同转化的同来源大鼠成纤维细胞中,源自所有三个CaM基因的转录本水平进行了定量。在所有这些细胞中检测到了五种CaM mRNA。令人惊讶的是,与对照细胞相比,许多被研究的细胞系中所有CaM mRNA的含量均降低,其中CaMI和CaMII转录本的变化最为明显。相比之下,通过放射免疫测定法确定,所有这些细胞系中的CaM蛋白水平均升高。这些结果表明,CaM合成的致癌上调发生在转录后。根据用于转化的癌基因不同,在所研究的细胞系中发现了不同浓度的几种CaM结合蛋白。然而,CaM的过表达似乎并未影响CaM结合蛋白的总体水平。