MMSP tumor cells expressing the EWS/ATF1 oncogene do not support cAMP-inducible transcription

Oncogene
K K Li, K A Lee

Abstract

Malignant Melanoma of Soft Parts (MMSP) is associated with the EWS/ATF1 fusion protein that arises due to chromosomal fusion of the Ewings Sarcoma oncogene (EWS) and the cellular transcription factor ATF1. EWS/ATF1 can activate several cAMP-inducible promoters, suggesting that cellular transformation in MMSP might involve constitutive activation of cAMP-inducible promoters. To assess this possibility we have examined the status of the cAMP-signaling pathway in the available MMSP-derived cell lines (DTC1 and Su-ccs-1) and find that both cell lines share several features. First, in contrast to previous effects observed in transient assays, three chromosomal promoters containing ATF binding sites are not constitutively activated by endogenous EWS/ATF1 in MMSP cells. Second, all the components that are known to be required for cAMP-inducible transcription are present. Third, phosphorylation of the cAMP-response-element-binding protein (CREB) can be efficiently induced by cAMP. Fourth, cAMP is unable to activate transcription, as assessed by a GAL4/ATF1 reporter assay and analysis of the c-fos and adenovirus early promoters. Thus, cell lines derived from MMSP have a block to cAMP-signaling that lies downstream of CREB phosphorylatio...Continue Reading

Citations

Jul 23, 1999·Current Opinion in Oncology·J L Bennicelli, F G Barr
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