Messenger RNAs under differential translational control in Ki-ras-transformed cells.
Microarrays have been used extensively to identify differential gene expression at the level of transcriptional control in oncogenesis. However, increasing evidence indicates that changes in translational control are critical to oncogenic transformation. This study identifies mRNA transcripts that are differentially regulated, primarily at the level of translation, in the immortalized human embryonic prostate epithelial cell line 267B1 and the v-Ki-ras-transformed counterpart by comparing total mRNA to polysome-bound mRNA by using Affymetrix oligonucleotide microarrays. Among the transcripts that were identified were those encoding proteins involved in DNA replication, cell cycle control, cell-to-cell interactions, electron transport, G protein signaling, and translation. Many of these proteins are known to contribute to oncogenesis or have the potential to contribute to oncogenesis. Differential expression of RNA-binding proteins and the presence of highly conserved motifs in the 5' and 3' untranslated regions of the mRNAs are consistent with multiple pathways and mechanisms governing the changes in translational control. Although Alu sequences were found to be associated with increased translation in transformed cells, an evolutionarily conserved motif was identified in the 3' untranslated regions of ephrinB1, calreticulin, integrin alpha3, and mucin3B that was associated with decreased polysome association in 267B1/Ki-ras.
Spence
Jean
J
Sidney Kimmel Cancer Center, San Diego, CA, USA. jlspence@san.rr.com
Duggan
Brendan M
BM
Eckhardt
Colleen
C
McClelland
Michael
M
Mercola
Dan
D
D020413:3' Untranslated Regions / Q000235:genetics; D020121:5' Untranslated Regions / Q000235:genetics; D020816:Amino Acid Motifs; D001483:Base Sequence; D002461:Cell Line, Transformed; D016384:Consensus Sequence; D015536:Down-Regulation / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D015689:Oncogene Protein p21(ras) / Q000235:genetics / Q000378:metabolism*; D011132:Polyribosomes; D014176:Protein Biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics* / Q000302:isolation & purification; D012334:RNA, Neoplasm; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000235:genetics
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D015689:Oncogene Protein p21(ras)