Leptin receptor expression and its association with PI3K/AKT signaling pathway in diffuse large B-cell lymphoma.
We investigated the role of the leptin receptor (Ob-R) and its relationship with PI3K/AKT activation in diffuse large B-cell lymphoma (DLBCL) clinical samples followed by in vitro studies using a panel of CRC cell lines. Leptin exerts its physiological action through its receptor Ob-R. Overexpression of Ob-R has been implicated in the pathogenesis of a variety of malignancies; however, its role in DLBCL has not been investigated. Using immunohistochemistry on a large cohort of DLBCL samples in a tissue microarray format, Ob-R immunostaining was detected in 86/216 (39.8%). Ob-R overexpression was associated with the catalytic subunit p110 of PI3K (p = 0.0283), activated AKT (p = 0.0003), and antiapoptotic marker XIAP (p = 0.0008) expression. In in vitro analysis using DLBCL cell lines, our data showed that leptin stimulated cell proliferation and inhibited apoptosis via activation of the PI3K/AKT signaling pathway. Pretreatment of DLBCL cells with Ob-R specific small interference RNA or inactivation of PI3K/AKT activity by LY294002 abolished these responses. Altogether, these data suggest that leptin plays a critical role in DLBCL pathogesis through the P13K/AKT pathway via Ob-R.
Uddin
Shahab
S
Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Bu
Rong
R
Ahmed
Maqbool
M
Hussain
Azhar R
AR
Ajarim
Dahish
D
Al-Dayel
Fouad
F
Bavi
Prashant
P
Al-kuraya
Khawla S
KS
D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D020738:Leptin / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D054411:Receptors, Leptin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D020738:Leptin; D034741:RNA, Small Interfering; D054411:Receptors, Leptin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt