Clinical significance of Phosphatidyl Inositol Synthase overexpression in oral cancer

BMC Cancer

Research Article

Jatinder Kaur¹  Meenakshi Sawhney¹  Ranju Ralhan²  Siddartha DattaGupta³  Anurag Srivastava⁴  Nootan K Shukla⁵ 

[1] Department of Biochemistry, All India Institute for Medical Sciences, Ansari Nagar, 110029, New Delhi, India;Department of Biochemistry, All India Institute for Medical Sciences, Ansari Nagar, 110029, New Delhi, India;Joseph & Mildred Sonshine Family Centre for Head & Neck Disease, Mount Sinai Hospital, USA;Department of Otolaryngology-Head and Neck Surgery, Mount Sinai Hospital, USA;Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Joseph & Wolf Lebovic Health Complex, 600 University Avenue, Room 6-500, M5G 1X5, Toronto, Ontario, Canada;Department of Otolaryngology-Head and Neck Surgery, University of Toronto, M5G 2N2, Toronto, Ontario, Canada;Department of Chemistry and Centre for Research in Mass Spectrometry, York University, CB- Room 246, 4700 Keele Street, M3J 1P3, Toronto, Ontario, Canada;Department of Pathology, All India Institute for Medical Sciences, Ansari Nagar, 110029, New Delhi, India;Department of Surgical Disciplines, All India Institute for Medical Sciences, Ansari Nagar, 110029, New Delhi, India;Department of Surgical Oncology, Institute of Rotary Cancer Hospital, All India Institute for Medical Sciences, Ansari Nagar, 110029, New Delhi, India;

关键词: Oral Cancer;    Oral Squamous Cell Carcinoma;    Oral Squamous Cell Carcinoma;    Smokeless Tobacco;    Oral Lesion;   

DOI  :  10.1186/1471-2407-10-168

 received in 2009-08-07, accepted in 2010-04-28,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundWe 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.MethodsTissue 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.ResultsSignificant 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.ConclusionCollectively, increased PI synthase expression was found to be an early event in oral cancer and a target for smokeless tobacco.

【 授权许可】

Unknown   
© Kaur et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.