Transcriptional down regulation of the nov proto-oncogene in fibroblasts transformed by p60v-src.
We have sought to identify genes whose expression is altered as a consequence of transformation by p60v-src. Using the mRNA differential display method, we have identified the nov proto-oncogene as one gene that is down regulated in chicken embryo fibroblasts (CEFs) transformed by p60v-src. nov transcripts were also found to be present at only very low levels in proliferating CEFs in comparison with quiescent CEFs. Serum stimulation of quiescent CEFs also resulted in a decline in the steady-state level of nov transcripts. Taken together, these findings suggest that the nov gene is expressed only in quiescent fibroblasts and that its down regulation may contribute to cellular transformation by the v-src oncogene. Down regulation of the nov gene appears to occur at both the transcriptional and posttranscriptional levels. Results obtained from experiments with a protein kinase inhibitor suggest that protein kinase C may be a key downstream effector in mediating the down regulation of nov transcripts in response to activation of p60src or serum stimulation. In addition, we found that transcription of an unknown gene is required for the decline in the steady-state level of nov transcripts in response to serum stimulation.
Scholz
G
G
Laboratory of Molecular Oncology, Rockefeller University, New York, New York 10021, USA.
Martinerie
C
C
Perbal
B
B
Hanafusa
H
H
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D002645:Chickens; D055513:Connective Tissue Growth Factor; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology; D015972:Gene Expression Regulation, Neoplastic; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics*; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000235:genetics*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic
D004791:Enzyme Inhibitors; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D007546:Isoquinolines; D015513:Oncogene Proteins; D009856:Oncogene Proteins, Viral; D010879:Piperazines; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D055513:Connective Tissue Growth Factor; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015688:Oncogene Protein pp60(v-src); D011493:Protein Kinase C