Clinical significance of phosphatidyl inositol synthase overexpression in oral cancer.
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.


CONCLUSIONS
Collectively, increased PI synthase expression was found to be an early event in oral cancer and a target for smokeless tobacco.
Kaur
Jatinder
J
Department of Biochemistry, All India Institute for Medical Sciences, Ansari Nagar, New Delhi-110029, India.
Sawhney
Meenakshi
M
Dattagupta
Siddartha
S
Shukla
Nootan K
NK
Srivastava
Anurag
A
Ralhan
Ranju
R
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D051607:CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000209:etiology / Q000235:genetics; D054337:Cell Dedifferentiation; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000378:metabolism; D004847:Epithelial Cells / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007972:Leukoplakia, Oral / Q000201:enzymology* / Q000209:etiology / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000209:etiology / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011230:Precancerous Conditions / Q000201:enzymology* / Q000209:etiology / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis; D014030:Tobacco, Smokeless / Q000009:adverse effects*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
C530104:CCND1 protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger; D019938:Cyclin D1; D019869:Phosphatidylinositol 3-Kinases; C496766:CDIPT protein, human; D051607:CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase