CLPTM1L is overexpressed in lung cancer and associated with apoptosis

PLoS One. 2012;7(12):e52598. doi: 10.1371/journal.pone.0052598. Epub 2012 Dec 26.

Abstract

CLPTM1L is believed to be associated with lung cancer. However, there is little information regarding its expression and function. Here using immunohistochemistry, we found that CLPTM1L expression was markedly increased in lung cancer tissues relative to normal tissues, especially in lung adenocarcinoma. CLPTM1L expression was not found to be associated with stages, smoking status, lymph node metastasis, or T lymphocyte infiltration but with differentiation stage. We found CLPTM1L to be enriched in the mitochondrial compared with plasma membrane protein extracts. CLPTM1L-EGFP transfection showed that the molecule product was expressed in cytoplasm and indicated the mitochondrial localization stained with mitochondrial marker MitoTracker. CLPTM1L transferred lung cancer cell line 95-D showed no growth inhibition or cell apoptosis, but it did show inhibited sensitivity to cis-diamminedichloroplatinum(II) (cisplatin, CDDP). Knockdown of CLPTM1L by RNAi did not interfere with cell proliferation but it did increase cell sensitivity to CDDP and activation of caspase-9 and caspase-3/7. These data indicate CLPTM1L is a mitochondria protein and that it may be associated with anti-apoptotic mechanism which affects drug-resistance in turn.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacology
  • Apoptosis*
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Drug Resistance, Neoplasm
  • Enzyme Activation / drug effects
  • Female
  • Gene Expression
  • Gene Knockdown Techniques
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Mitochondria / metabolism
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Protein Transport
  • RNA, Small Interfering / genetics
  • Sequence Analysis, DNA

Substances

  • Antineoplastic Agents
  • CLPTM1L protein, human
  • Membrane Proteins
  • Neoplasm Proteins
  • RNA, Small Interfering
  • Caspases
  • Cisplatin

Grants and funding

This work was supported by the Shanghai Science and Technology Committee (No.09JC1412900, No.10411969100), the Shanghai Educational Committee (No.10YZ54), the Shanghai Putuo District Science and Technology Committee (2010), and the Innovation Program of Shanghai Municipal Education commission (13ZZ096). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.