Pancreatic cancer is a lethal disease with a propensity for invading and metastasizing into the surrounding tissues, including the liver and intestines. A number of factors are aberrantly overexpressed in this tumor type and actively promote cancer progression and metastasis. The present study demonstrates that paired box transcription factor 6 (PAX6) and C-X-C chemokine receptor 4 (CXCR4) are frequently co-expressed in primary pancreatic adenocarcinoma tumors and established cell lines. Expression analysis methods used in the present study included evaluation of protein expression by western blot analysis and immunofluorescence, transcript expression levels by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and luciferase assays utilizing regulatory elements from the CXCR4 gene locus. Canonical PAX6 and alternative splice variant PAX6(5a) proteins are expressed in pancreatic cancer and can drive gene expression through a conserved enhancer element within the first intron of the CXCR4 gene. As demonstrated by the introduction of an exogenous reporter construct with or without the intronic enhancer, loss of this element inhibited gene expression within numerous pancreatic cancer cell lines including Panc1, MIA-PaCa2 and BxPC3. All of the pancreatic cancer cell lines expressed the canonical CXCR4B transcript in addition to the alternatively spliced variant CXCR4A as determined by RT-qPCR experiments. The discovery of variant transcripts in pancreatic cancer cells may provide new candidates for future targeted therapies.
Keywords: C-X-C chemokine receptor 4; CXCR4 transcript variant A; CXCR4 transcript variant B; PAX6 exon 5 alternative transcript variant; alternative splice variants; paired box transcription factor 6; pancreatic cancer.