Lipoprotein lipase is frequently overexpressed or translocated in cervical squamous cell carcinoma and promotes invasiveness through the non-catalytic C terminus
British Journal of Cancer, 07/13/2012
Carter SA et al. – This is the first demonstration of an expressed fusion gene in cervical SCC. Overexpressed wild-type or translocated LPL is a candidate for targeted therapy.Methods
- The rearranged genes were identified by breakpoint mapping, long-range PCR and sequencing.
- We investigated gene expression in vivo using reverse-transcription PCR and tissue microarrays, and studied the phenotypic consequences of forced gene overexpression.
- The rearrangement involved lipoprotein lipase (LPL) and peroxisome biogenesis factor-5 (PEX5).
- Whereas LPL–PEX5 was expressed at low levels and contained a premature stop codon, PEX5–LPL was highly expressed and encoded a full-length chimeric protein (including the majority of the LPL coding region).
- Consistent with these findings, PEX5 was constitutively expressed in normal cervical squamous cells, whereas LPL expression was negligible.
- The LPL gene was rearranged in 1 out of 151 cervical SCCs, whereas wild-type LPL overexpression was common, being detected in 10 out of 28 tissue samples and 4 out of 10 cell lines.
- Forced overexpression of wild-type LPL and PEX5–LPL fusion transcripts resulted in increased invasiveness in cervical SCC cells, attributable to the C-terminal non-catalytic domain of LPL, which was retained in the fusion transcripts.