PAX6 is expressed in pancreatic cancer and actively participates in cancer progression through activation of the MET tyrosine kinase receptor gene

Joseph B. Mascarenhas, Kacey P. Young, Erica L. Littlejohn, Brian K. Yoo, Ravi Salgia, Deborah Lang

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Tumors of the exocrine pancreas have a poor prognosis. Several proteins are overexpressed in this cancer type, including the MET tyrosine kinase receptor and the transcription factor PAX6. In this report, we find that PAX6(5a), an alternately spliced variant form of PAX6, is expressed in pancreatic carcinoma cell lines at higher levels than the canonicalPAX6protein. Both protein forms of PAX6 bind directly to an enhancer element in the MET promoter and activate the expression of the METgene. In addition, inhibition of PAX6 transcripts leads to a decline in cell growth and survival, differentiation, and a concurrent reduction of MET protein expression. These data support a model for a neoplastic pathway, where expression of a transcription factor from development activates the MET receptor, a protein that has been directly linked to protumorigenic processes of resisting apoptosis, tumor growth, invasion, and metastasis.

Original languageEnglish (US)
Pages (from-to)27524-27532
Number of pages9
JournalJournal of Biological Chemistry
Volume284
Issue number40
DOIs
StatePublished - Oct 2 2009
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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