Gene expression profiling of fibroblasts resistant toward oncogene-mediated transformation reveals preferential transcription of negative growth regulators

被引:21
作者
Tchernitsa, OI
Zuber, J
Sers, C
Brinckmann, R
Britsch, SK
Adams, V
Schäfer, R
机构
[1] Humboldt Univ, Charite, Inst Pathol, Lab Mol Tumour Pathol, D-10117 Berlin, Germany
[2] Univ Zurich, Inst Pathol, CH-8091 Zurich, Switzerland
[3] Univ Leipzig, Ctr Cardiol, D-04289 Leipzig, Germany
关键词
suppression subtractive hybridization; RAS; preneoplastic phenotype; tumour suppressor genes;
D O I
10.1038/sj.onc.1202987
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The signal-transducing Res proteins are important driving forces of diverse cellular processes such as proliferation, neoplastic transformation, differentiation and growth inhibition. As a step toward understanding the complex mechanisms underlying cellular responses, gene expression patterns were examined in two phenotypically normal fibroblast lines which differ in their sensitivity toward oncogene-mediated transformation. Suppression subtractive hybridization (SSH) was used to establish a subtracted cDNA library specific for the REF52 cell line which, like normal diploid fibroblasts, is refractory toward neoplastic transformation induced by mutated HRAS oncogenes, In contrast, rat 208F control cells can be efficiently transformed by HRAS. The nucleotide sequence of 549 subtracted cDNA clones ('REF52 minus 208F') was determined. We identified 93 preferentially expressed gene fragments in resistant REF52 cells as compared to 208F cells, Seventeen of the 52 known genes (32.6%) are capable of inhibiting cell proliferation or of adversely affecting oncogenic signal transduction pathways. These results suggest that the anti-oncogenic properties of resistant REF52 cells are determined by multiple negative growth regulators. The preneoplastic state expressed in 208F cells is characterized by impairment of unexpectedly redundant control mechanisms. Our results also demonstrate that SSH is a powerful method for identifying specific transcriptional patterns in closely related cell types.
引用
收藏
页码:5448 / 5454
页数:7
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