Overexpression of leptin receptor predicts an unfavorable outcome in Middle Eastern ovarian cancer

Uddin, Shahab; Bu, Rong; Ahmed, Maqbool; Abubaker, Jehad; Al‐Dayel, Fouad; Bavi, Prashant; Al‐Kuraya, Khawla S.

doi:10.1186/1476-4598-8-74

Cited by 100 publications

(103 citation statements)

References 36 publications

(37 reference statements)

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“…13 Diverse cancer cells derived from different tissues, such as brain, breast, colon or prostate, were reported to have ObR expression. [21][22][23][24][25] Furthermore, Ob-R overexpression not only correlated with the degree of malignancy, but also was an independent prognostic variable to predict poor progression-free survival in brain tumor, ovarian cancer, and breast cancer, 24,26,27 which suggested that ObR+ cells might be closely related with tumor initiation and development. In this study, we claimed that ObR+ glioblastoma cells presented chemoresistance, which showed that TMZ could not inhibit cell proliferation and could not induce apoptosis effectively.…”

Section: Discussionmentioning

confidence: 99%

High expression of leptin receptor leads to temozolomide resistance with exhibiting stem/progenitor cell features in gliobalastoma

et al. 2013

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Section: Discussionmentioning

confidence: 99%

High expression of leptin receptor leads to temozolomide resistance with exhibiting stem/progenitor cell features in gliobalastoma

et al. 2013

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“…In addition, serum leptin levels are higher in patients diagnosed with endometrial and ovarian cancer compared to those observed in healthy individuals (14)(15)(16). Furthermore, in vitro studies on human cell lines of ovarian and endometrial cancer indicate that leptin leads to the activation of signaling pathways, such as JAK2̸STAT3, MAPK̸ERK and PI3K̸AKT, which stimulate cell proliferation and inhibit apoptosis (17,18), demonstrating its biological ability to promote the malignant behavior of cancers by stimulating growth, migration and invasiveness of tumor cells (19). Those effects are exerted via its binding to its protein receptor (Ob-R), which belongs to the class I cytokine receptor family (20).…”

Section: Introductionmentioning

confidence: 99%

Expression of leptin receptor in endometrial biopsies of endometrial and ovarian cancer patients

et al. 2013

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Abstract. The adipokine leptin plays a critical role in the regulation of reproductive function and there has been growing interest in its potential role in the development of cancers in which obesity is an established risk factor. Serum leptin levels were found to be higher in patients diagnosed with endometrial and ovarian cancer compared to those observed in healthy individuals. This study was conducted to determine the expression of the leptin receptor (Ob-R) in endometrial biopsies of patients diagnosed with endometrial and ovarian cancer. In this preliminary study, immunohistochemistry (IHC) and the color deconvolution method were used to assess the expression levels of the Ob-R protein in three groups of endometrial tissue: one from patients diagnosed with endometrioid endometrial carcinoma, one from patients diagnosed with ovarian cancer and one from individuals without any diagnosed gynecologic disease (control group). Our results demonstrated that the highest expression of Ob-R protein in endometrial biopsies was detected in the ovarian cancer group (P=0.000). This finding suggests that changes in Ob-R expression may be assessed through the measurement of the optical density of endometrial biopsies and may become a useful tool in preventive screening, particularly for ovarian cancer.

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“…14,23-25 p-AKT, BCL-XL, and XIAP were scored as described previously. 26,27 Statistical Analysis The JMP7 (SAS Institute, Cary, NC, USA) software package was used for data analyses. Survival curves were generated using the Kaplan-Meier method, with significance evaluated using the Mantel-Cox log-rank test.…”

Section: Immunohistochemistrymentioning

confidence: 99%

HGF/c-Met pathway has a prominent role in mediating antiapoptotic signals through AKT in epithelial ovarian carcinoma

Uddin

Bavi

et al. 2011

Laboratory Investigation

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The Met receptor tyrosine kinase and its ligand, hepatocyte growth factor (HGF), are overexpressed and/or activated in a variety of human malignancies. However, its role in epithelial ovarian carcinoma (EOC) has not been clearly elucidated. Therefore, we investigated the role of HGF/c-Met signaling pathway in a large series (156) of Saudi EOC patient samples, a panel of cell lines, and xenografts in a NUDE mouse model. Using immunohistochemistry, c-Met overexpression was found in 27.2% Middle Eastern EOC samples and was associated with an advanced tumor stage (P ¼ 0.0187). c-Met overexpression was also associated with antiapoptotic markers X-chromosome-linked inhibitors of apoptosis (XIAP) (P ¼ 0.0008) and Bcl-XL (P ¼ 0.0493) expression. Treatment of EOC cell lines with PHA665752 causes a dose-dependent inhibition of cell viability and induction of apoptosis. Furthermore, PHA665752 treatment causes dephosphorylation of AKT and downregulation of antiapoptotic proteins XIAP and Bcl-XL. In addition, PHA665752-induced apoptosis occurs through activation of Bax-mediated release of cytochrome c and activation of caspases. Finally, co-treatment of EOC with PHA665752 and cisplatin causes augmented effect on apoptosis of EOC cells and resulted in synergistic inhibition of EOC xenograft tumor growth in NUDE mice. These results indicate that c-Met/HGF pathway may be a potential target for therapeutic intervention for treatment of EOC.

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Overexpression of leptin receptor predicts an unfavorable outcome in Middle Eastern ovarian cancer

Cited by 100 publications

References 36 publications

High expression of leptin receptor leads to temozolomide resistance with exhibiting stem/progenitor cell features in gliobalastoma

High expression of leptin receptor leads to temozolomide resistance with exhibiting stem/progenitor cell features in gliobalastoma

Expression of leptin receptor in endometrial biopsies of endometrial and ovarian cancer patients

HGF/c-Met pathway has a prominent role in mediating antiapoptotic signals through AKT in epithelial ovarian carcinoma

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