Mmsp tumor cells expressing the ews/atf1 oncogene do not support camp-inducible transcription

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 phosphorylation. In light of the

cAMP-responsiveness of almost all mammalian cell types, our findings suggest that the inability to respond to cAMP might be an important feature of MMSP cells. Access through your

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BEING VIEWED BY OTHERS THE ONCOGENIC PROPERTIES OF THE _EWSR1::CREM_ FUSION GENE ARE ASSOCIATED WITH POLYAMINE METABOLISM Article Open access 25 March 2023 STAT3 PROMOTES MELANOMA METASTASIS

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EWING SARCOMA Article Open access 03 August 2021 AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Biology, Hong Kong University of Science & Technology, Clear Water Bay,

Kowloon, Hong Kong, P.R.C Kim KC Li & Kevin AW Lee Authors * Kim KC Li View author publications You can also search for this author inPubMed Google Scholar * Kevin AW Lee View author

publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Li, K., Lee, K. MMSP tumor cells

expressing the EWS/ATF1 oncogene do not support cAMP-inducible transcription. _Oncogene_ 16, 1325–1331 (1998). https://doi.org/10.1038/sj.onc.1201649 Download citation * Received: 27 June

1997 * Revised: 14 October 1997 * Accepted: 14 October 1997 * Published: 19 March 1998 * Issue Date: 12 March 1998 * DOI: https://doi.org/10.1038/sj.onc.1201649 SHARE THIS ARTICLE Anyone you

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Springer Nature SharedIt content-sharing initiative KEYWORDS * EWS/ATF1 * cAMP * oncogene * phosphorylation