Gene amplification and associated loss of 5′ regulatory sequences of CoAA in human cancers

Y. Sui, Z. Yang, Jin-Xiong She, L. Zhang, K. L. Blanchard, S. C. Peiper, W. S. Dynan, Dorothy Tuan Lo, L. Ko

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

CoAA is an RRM-containing transcriptional coactivator that stimulates transcriptional activation and regulates alternative splicing. We show that the CoAA gene is amplified at the chromosome 11q13 locus in a subset of primary human cancers including non-small cell lung carcinoma, squamous cell skin carcinoma and lymphoma. Analysis of 42 primary tumors suggests that CoAA amplifies independently from the CCND1 locus. Detailed mapping of three CoAA amplicons reveals that the amplified CoAA gene is consistently located at the 5′ boundaries of the amplicons. The CoAA coding and basal promoter sequences are retained within the amplicons but upstream silencing sequences are lost. CoAA protein is overexpressed in tumors containing the amplified CoAA gene. RNA dot blot analysis of 100 cases of primary tumors suggests elevated CoAA mRNA expression. CoAA positively regulates its own basal promoter in transfection assays. Thus, gene amplification, loss of silencing sequence and positive feedback regulation may lead to drastic upregulation of CoAA protein. CoAA has transforming activities when tested in soft agar assays, and CoAA is homologous to oncoproteins EWS and TLS, which regulate alternative splicing. These data imply that CoAA may share a similar oncogenic mechanism with oncogene EWS and that CoAA deregulation may alter the alternative splicing of target genes.

Original languageEnglish (US)
Pages (from-to)822-835
Number of pages14
JournalOncogene
Volume26
Issue number6
DOIs
StatePublished - Feb 8 2007

Fingerprint

Gene Amplification
Alternative Splicing
Genes
Neoplasms
Oncogene Proteins
Oncogenes
Non-Small Cell Lung Carcinoma
Transcriptional Activation
Agar
Transfection
Squamous Cell Carcinoma
Lymphoma
Proteins
Up-Regulation
Chromosomes
RNA
Messenger RNA
Skin

Keywords

  • CoAA oncogene
  • Gene amplification
  • Transcriptional coactivator

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Sui, Y., Yang, Z., She, J-X., Zhang, L., Blanchard, K. L., Peiper, S. C., ... Ko, L. (2007). Gene amplification and associated loss of 5′ regulatory sequences of CoAA in human cancers. Oncogene, 26(6), 822-835. https://doi.org/10.1038/sj.onc.1209847

Gene amplification and associated loss of 5′ regulatory sequences of CoAA in human cancers. / Sui, Y.; Yang, Z.; She, Jin-Xiong; Zhang, L.; Blanchard, K. L.; Peiper, S. C.; Dynan, W. S.; Tuan Lo, Dorothy; Ko, L.

In: Oncogene, Vol. 26, No. 6, 08.02.2007, p. 822-835.

Research output: Contribution to journalArticle

Sui, Y, Yang, Z, She, J-X, Zhang, L, Blanchard, KL, Peiper, SC, Dynan, WS, Tuan Lo, D & Ko, L 2007, 'Gene amplification and associated loss of 5′ regulatory sequences of CoAA in human cancers', Oncogene, vol. 26, no. 6, pp. 822-835. https://doi.org/10.1038/sj.onc.1209847
Sui, Y. ; Yang, Z. ; She, Jin-Xiong ; Zhang, L. ; Blanchard, K. L. ; Peiper, S. C. ; Dynan, W. S. ; Tuan Lo, Dorothy ; Ko, L. / Gene amplification and associated loss of 5′ regulatory sequences of CoAA in human cancers. In: Oncogene. 2007 ; Vol. 26, No. 6. pp. 822-835.
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