Lipoprotein lipase is frequently overexpressed or translocated in cervical squamous cell carcinoma and promotes invasiveness through the non-catalytic C terminus.
BACKGROUND
We studied the biological significance of genes involved in a novel t(8;12)(p21.3;p13.31) reciprocal translocation identified in cervical squamous cell carcinoma (SCC) cells.


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.


RESULTS
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.


CONCLUSIONS
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.
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
S A
SA
Carter
N A
NA
Foster
C G
CG
Scarpini
A
A
Chattopadhyay
M R
MR
Pett
I
I
Roberts
N
N
Coleman
D000328:Adult; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002384:Catalysis; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D012313:RNA / Q000032:analysis; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
D012313:RNA; D008071:Lipoprotein Lipase