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Signaling properties and expression in normal and tumor tissues of two phospholipase C epsilon splice variants

Oncogene volume 24, pages 90–100 (2005)Cite this article

Abstract

Phospholipase Cɛ (PLCɛ) is a novel member of phosphoinositide-specific phospholipase C enzymes with a unique regulatory link to Ras GTP-ases. In the present studies, we establish existence of two splice variants (PLCɛ1a and PLCɛ1b) derived from human PLCɛ1 gene. When expressed in COS or HEK293 cells, PLCɛ1a and PLCɛ1b have similar potential to be stimulated by diverse signaling pathways via tyrosine kinase and G-protein coupled receptors and share the ability to function as an effector of Ras. The expression pattern shows broader mRNA expression of PLCɛ1a in normal tissues; furthermore, in most cell lines expressing PLCɛ, PLCɛ1a is the only splice variant present. Analysis of normal/tumor matched pairs derived from colon and rectum demonstrates greatly reduced expression levels in tumor tissues. Further studies in a colorectal tumor cell line lacking PLCɛ show restoration of transcription of PLCɛ1a and PLCɛ1b by demethylating agent 5-aza-2′-deoxycytidine, suggesting epigenetic silencing through hypermethylation. In addition, expression of exogenous PLCɛ in this cell line demonstrates inhibitory effects of PLCɛ on cell viability and proliferation. Taken together, our findings suggest that regulatory mechanisms controlling expression of PLCɛ, broadened by diversity introduced by splice variants, could play important role in PLCɛ regulation in normal and tumor cells.

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Acknowledgements

We are grateful to T Kataoka for pcDNA3.1GFP-PLCɛ and antibodies to PLCɛ, J Lomasney for pCMVmycPLCɛ, G Kelley for pCMVPLCɛ-Flag, R Marais for pEFmyCRaf and C Marshall for plasmids encoding H-Ras. We would also like to thank N Gandarillas and M Josephs for their valuable assistance. This work is funded by an Institute of Cancer Research studentship to SCS and a Cancer Research UK grant to MK.

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  1. Cancer Research UK Centre for Cell and Molecular Biology, Chester Beatty Laboratories, The Institute of Cancer Research, Fulham Road, London, SW3 6JB, UK

    Sonia Caroline Sorli, Tom D Bunney, Hugh F Paterson & Matilda Katan

  2. National Heart and Lung Institute Division, Faculty of Medicine, Imperial College London, Armstrong Road, London, SW7 2AZ, UK

    Peter H Sugden

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  1. Sonia Caroline Sorli
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  2. Tom D Bunney
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Correspondence to Matilda Katan.

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Sorli, S., Bunney, T., Sugden, P. et al. Signaling properties and expression in normal and tumor tissues of two phospholipase C epsilon splice variants. Oncogene 24, 90–100 (2005). https://doi.org/10.1038/sj.onc.1208168

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