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

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 canonical PAX6 protein. Both protein forms of PAX6 bind directly to an enhancer element in the MET promoter and activate the expression of the MET gene. 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.
Authors	Joseph B Mascarenhas, Kacey P Young, Erica L Littlejohn, Brian K Yoo, Ravi Salgia, Deborah Lang
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 284 Issue 40 Pg. 27524-32 (Oct 02 2009) ISSN: 1083-351X [Electronic] United States
PMID	19651775 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Eye Proteins Homeodomain Proteins PAX6 Transcription Factor PAX6 protein, human Paired Box Transcription Factors Pax6 protein, mouse Proto-Oncogene Proteins Receptors, Growth Factor Repressor Proteins MET protein, human Proto-Oncogene Proteins c-met
Topics	Adenocarcinoma (genetics, pathology) Animals Apoptosis (genetics) Base Sequence Cell Line, Tumor Disease Progression Eye Proteins (genetics) Gene Expression Regulation, Neoplastic Genes, Reporter Homeodomain Proteins (genetics) Humans Mice Molecular Sequence Data Mutation Neoplasm Metastasis (genetics) PAX6 Transcription Factor Paired Box Transcription Factors (deficiency, genetics) Pancreatic Neoplasms (genetics, pathology) Phenotype Proto-Oncogene Proteins (genetics) Proto-Oncogene Proteins c-met Receptors, Growth Factor (genetics) Repressor Proteins (genetics) Transcriptional Activation

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