Clinical significance of phosphatidyl inositol synthase overexpression in oral cancer

BMC Cancer. 2010 Apr 28;10:168. doi: 10.1186/1471-2407-10-168.

Abstract

Background: We reported increased levels of phosphatidyl inositol synthase (PI synthase), (enzyme that catalyses phosphatidyl inositol (PI) synthesis-implicated in intracellular signaling and regulation of cell growth) in smokeless tobacco (ST) exposed oral cell cultures by differential display. This study determined the clinical significance of PI synthase overexpression in oral squamous cell carcinoma (OSCC) and premalignant lesions (leukoplakia), and identified the downstream signaling proteins in PI synthase pathway that are perturbed by smokeless tobacco (ST) exposure.

Methods: Tissue microarray (TMA) Immunohistochemistry, Western blotting, Confocal laser scan microscopy, RT-PCR were performed to define the expression of PI synthase in clinical samples and in oral cell culture systems.

Results: Significant increase in PI synthase immunoreactivity was observed in premalignant lesions and OSCCs as compared to oral normal tissues (p = 0.000). Further, PI synthase expression was significantly associated with de-differentiation of OSCCs, (p = 0.005) and tobacco consumption (p = 0.03, OR = 9.0). Exposure of oral cell systems to smokeless tobacco (ST) in vitro confirmed increase in PI synthase, Phosphatidylinositol 3-kinase (PI3K) and cyclin D1 levels.

Conclusion: Collectively, increased PI synthase expression was found to be an early event in oral cancer and a target for smokeless tobacco.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blotting, Western
  • CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase / genetics
  • CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase / metabolism*
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / etiology
  • Carcinoma, Squamous Cell / genetics
  • Cell Dedifferentiation
  • Cell Line, Tumor
  • Cyclin D1 / metabolism
  • Epithelial Cells / enzymology*
  • Epithelial Cells / pathology
  • Humans
  • Immunohistochemistry
  • Leukoplakia, Oral / enzymology*
  • Leukoplakia, Oral / etiology
  • Leukoplakia, Oral / genetics
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Microscopy, Confocal
  • Middle Aged
  • Mouth Neoplasms / enzymology*
  • Mouth Neoplasms / etiology
  • Mouth Neoplasms / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Precancerous Conditions / enzymology*
  • Precancerous Conditions / etiology
  • Precancerous Conditions / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Array Analysis
  • Tobacco, Smokeless / adverse effects*
  • Tumor Cells, Cultured
  • Up-Regulation

Substances

  • CCND1 protein, human
  • Membrane Proteins
  • RNA, Messenger
  • Cyclin D1
  • Phosphatidylinositol 3-Kinases
  • CDIPT protein, human
  • CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase