By the same authors

From the same journal

From the same journal

Human prostate cell lines from normal and tumourigenic epithelia differ in the pattern and control of choline lipid headgroups released into the medium on stimulation of protein kinase C

Research output: Contribution to journalArticle

Published copy (DOI)

Author(s)

  • M. Rumsby
  • J. Schmitt
  • M. Sharrard
  • G. Rodrigues
  • M. Stower
  • N. Maitland

Department/unit(s)

Publication details

JournalBritish journal of cancer
DatePublished - 15 Feb 2011
Issue number4
Volume104
Number of pages12
Pages (from-to)673-684
Original languageEnglish

Abstract

BACKGROUND: Expression of protein kinase C alpha (PKC alpha) is elevated in prostate cancer (PCa); thus, we have studied whether the development of tumourigenesis in prostate epithelial cell lines modifies the normal pattern of choline (Cho) metabolite release on PKC activation.

METHODS: Normal and tumourigenic human prostate epithelial cell lines were incubated with [H-3]-Cho to label choline phospholipids. Protein kinase C was activated with phorbol ester and blocked with inhibitors. Choline metabolites were resolved by ion-exchange chromatography. Phospholipase D (PLD) activity was measured by transphosphatidylation. Protein expression was detected by western blotting and/or RT-PCR. Choline uptake was measured on cells in monolayers over 60 min.

RESULTS: Normal prostate epithelial cell lines principally released phosphocholine (PCho) in contrast to tumourigenic lines, which released Cho. In addition, only with normal cell lines did PKC activation stimulate Cho metabolite release. Protein kinase C alpha expression varied between normal and tumourigenic cell lines but all showed a PKCa link to myristoylated alanine-rich C kinase substrate (MARCKS) protein. The five cell lines differed in Cho uptake levels, with normal PNT2C2 line cells showing highest uptake over 60 min incubation. Normal and tumourigenic cell lines expressed mRNA for PLD1 and PLD2, and showed similar levels of basal and PKC-activated PLD activity.

CONCLUSIONS: The transition to tumourigenesis in prostate epithelial cell lines results in major changes to Cho metabolite release into the medium and PKC signalling to phosphatidylcholine turnover. The changes, which reflect the metabolic and proliferative needs of tumourigenic cells compared with untransformed cells, could be significant for both diagnosis and treatment. British Journal of Cancer (2011) 104, 673-684. doi:10.1038/sj.bjc.6606077 www.bjcancer.com Published online 25 January 2011 (C) 2011 Cancer Research UK

    Research areas

  • prostate epithelial cell lines, protein kinase C, phospholipase D, choline and phosphocholine release, MARCKS, PHOSPHOLIPASE-D ACTIVITY, OVARIAN-CANCER CELLS, NIH 3T3 FIBROBLASTS, P70 S6 KINASE, PHORBOL ESTER, BREAST-CANCER, PHOSPHATIDYLCHOLINE BREAKDOWN, DEPENDENT MECHANISM, FUNCTIONAL-ROLE, GROWTH-FACTORS

Discover related content

Find related publications, people, projects, datasets and more using interactive charts.

View graph of relations