Mect1-Maml2 fusion oncogene linked to the aberrant activation of cyclic AMP/CREB regulated genes

Amy Coxon, Ester Rozenblum, Yoon Soo Park, Nina Joshi, Junji Tsurutani, Phillip A. Dennis, Ilan R. Kirsch, Frederic J. Kaye

Research output: Contribution to journalArticlepeer-review


Malignant salivary gland tumors can arise from a t(11;19) translocation that fuses 42 residues from Mect1/Torc1, a cyclic AMP (cAMP)/cAMP-responsive element binding protein (CREB)-dependent transcriptional coactivator, with 982 residues from Maml2, a NOTCH receptor coactivator. To determine if the Mect1-Maml2 fusion oncogene mediates tumorigenicity by disrupting cAMP/CREB signaling, we have generated in-frame deletions within the CREB-binding domain of Mect1/Torc1 for testing transformation activity and have also developed a doxycycline-regulated Mect1-Maml2 mammalian expression vector for global gene expression profiling. We observed that small deletions within the CREB-binding domain completely abolished transforming activity in RK3E epithelial cells. Further, we have shown that the ectopic induction of Mect1-Maml2 in HeLa cells strongly activated the expression of a group of known cAMP/CREB-regulated genes. In addition, we detected candidate cAMP-responsive element sites within 100 nucleotides of the transcriptional start sites of other genes activated by Mect1-Maml2 expression. In contrast, we did not observe alterations of known Notch-regulated target genes in these expression array profile experiments. We validated the results by reverse transcription-PCR in transfected HeLa, RK3E, and H2009 lung tumor cells and in mucoepidermoid cancer cells that endogenously express the fusion oncopeptide. Whereas overexpression of components of the cAMP pathway has been associated with a subset of human carcinomas, these data provide a direct genetic link between deregulation of cAMP/ CREB pathways and epithelial tumorigenesis and suggest future therapeutic strategies for this group of salivary gland tumors.

Original languageEnglish (US)
Pages (from-to)7137-7144
Number of pages8
JournalCancer Research
Issue number16
StatePublished - Aug 15 2005
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'Mect1-Maml2 fusion oncogene linked to the aberrant activation of cyclic AMP/CREB regulated genes'. Together they form a unique fingerprint.

Cite this