Enhanced Leptin Receptor Expression Identifies an Aggressive Subset of Middle Eastern Papillary Thyroid Cancer

Prashant Bavi, Abdul Siraj, Maha Al Rasheed, Devarajan Sriraman, Valerie Lopez, Valorie Balde, Mohammed Ahmed, Tarek Amin, Maqbool Ahmed, Rong Bu, Shahab Uddin, Khawla Al Kuraya

Research output: Contribution to conferencePoster

Abstract

A number of studies published recently focused on putative role of leptin in the pathogenesis of various primary human malignancies. However, the role of leptin and leptin receptor (Ob-R) in papillary thyroid cancer (PTC) has not yet been evaluated. The current study was aimed first at investigating Ob-R protein expression, and its clinicopathological correlation in a large cohort of Middle Eastern PTC. Then we investigated the effect of leptin on proliferation and apoptosis of PTC cells and the early signaling events involved. Ob-R immunostaining was detected in 410/512 (80.1 %) PTCs. PTCs that overexpressed Ob-R showed a aggressive phenotype characterized by older age, extrathyroid extension, larger tumor size, nodal metastasis, advanced stage and tall cell variant histologic subtype (p=0.0005, p=0.0006, p=0.0398, p= 0.0004, p=0.0111and p= 0.0003 respectively). Further PTCs with overexpression of Ob-R showed a significant direct association with overexpression of leptin (p=0.0004), XIAP (p<0.0001) and BCL-XL (p<0.0001). Interestingly, PTCs with Ob-R overexpression showed a statistically significant poor disease free survival (p=0.0235) as compared to PTCs with low expression of Ob-R. In vitro analysis showed that leptin stimulated cell proliferation and inhibit apoptosis via activation of phosphatidylinositol 3\#8217; kinase (PI3K)/AKT signaling pathway. The proliferation and anti-apoptotic effects of leptin were abolished by inhibition of Ob-R with small interference RNA (siRNA) and PI3K/AKT with LY294.So our data showed that Ob-R is commonly expressed in Middle Eastern PTC and leptin stimulates proliferation inhibits apoptosis in human PTC via PI3K/AKT pathway activation. These effects of leptin provide a link between obesity and PTC and may represent a target for anti cancer drug development.
Original languageEnglish
Publication statusPublished - 2009
EventAmerican Association for Cancer Research - DENVER, COLORADO, United States
Duration: 18 Apr 200922 Apr 2009

Conference

ConferenceAmerican Association for Cancer Research
Abbreviated titleAACR
CountryUnited States
CityCOLORADO
Period18/04/0922/04/09

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    Bavi, P., Siraj, A., Al Rasheed, M., Sriraman, D., Lopez, V., Balde, V., Ahmed, M., Amin, T., Ahmed, M., Bu, R., Uddin, S., & Al Kuraya, K. (2009). Enhanced Leptin Receptor Expression Identifies an Aggressive Subset of Middle Eastern Papillary Thyroid Cancer. Poster session presented at American Association for Cancer Research, COLORADO, United States.