Enhanced expression of peroxisome proliferator-activated receptor gamma in epithelial ovarian carcinoma

Abstract

The peroxisome proliferator-activated receptors (PPARs) belong to a subclass of nuclear hormone receptor that executes important cellular transcriptional functions. Previous studies have demonstrated the expression of PPARg in several tumours including colon, breast, bladder, prostate, lung and stomach. This study demonstrates the relative expression of PPARg in normal ovaries and different pathological grades of ovarian tumours of serous, mucinous, endometrioid, clear cell and mixed subtypes. A total of 56 ovarian specimens including 10 normal, eight benign, 10 borderline, seven grade 1, nine grade 2 and 12 grade 3 were analysed using immunohistochemistry. Immunoreactive PPARg was not expressed in normal ovaries. Out of eight benign and 10 borderline tumours, only one tumour in each group showed weak cytoplasmic PPARg expression. In contrast, 26 out of 28 carcinomas studied were positive for PPARg expression with staining confined to cytoplasmic and nuclear regions. An altered staining pattern of PPARg was observed in high-grade ovarian tumours with PPARg being mostly localized in the nuclei with little cytoplasmic immunoreactivity. On the other hand, predominant cytoplasmic staining was observed in lower-grade tumours. Significantly increased PPARg immunoreactivity was observed in malignant ovarian tumours (grade 1, 2 and 3) compared to benign and borderline tumours (w 2 ¼ 48.80, Po0.001). Western blot analyses showed significant elevation in the expression of immunoreactive PPARg in grade 3 ovarian tumours compared with that of normal ovaries and benign ovarian tumours (Po0.01). These findings suggest an involvement of PPARg in the onset and development of ovarian carcinoma and provide an insight into the regulation of this molecule in the progression of the disease.

An immunohistochemical perspective of PPARβ and one of its putative targets PDK1 in normal ovaries, benign and malignant ovarian tumours

“…of ovarian carcinoma (Zhang et al, 2005). We have also demonstrated enhanced expression of ILK, a putative target gene of PPARb, in high-grade ovarian tumours (Ahmed et al, 2003) and the presence of cell-free irILK in the serum and ascites of ovarian cancer patients (Ahmed et al, 2004).…”

Thiazolidinediones inhibit hepatocarcinogenesis in hepatitis B virus–transgenic mice by peroxisome proliferator‐activated receptor γ–independent regulation of nucleophosmin†

“…Moreover, in human pancreatic and ovarian cancers expression profiles indicate a strong overexpression of PPARc that positively correlate with higher pT stages and higher tumor grade. 29,30 Interestingly, our experiments showed that in Tg(HBV)CreKOc mice TZD administration inhibits tumor formation with a potency significantly higher than in parental and control mice. Moreover, PPARc ectopic expression in PPARc-deficient hepatocytes reduced the antiproliferative effect of TZD (Supporting Information Fig.…”

PGC-1α induces apoptosis in human epithelial ovarian cancer cells through a PPARγ-dependent pathway

“…Since this antagonist has some off-target activity, we sup- pressed PPARγ expression by siRNA, and found that this also inhibited PGC-1α-induced apoptosis in Ho-8910 cells, supporting our interpretation that PGC-1α exerted its effect through a PPARγ-dependent pathway. Although PPARγ is upregulated in epithelial ovarian carcinoma [23], the downregulation of PGC-1α in epithelial ovarian cancer may restrain the activation of PPARγ-dependent apoptotic pathway, which could indirectly contribute to the development of ovarian tumor. However, the detailed molecular mechanisms need further study.…”

“…Recent report shows that the expression of PPARγ is significantly enhanced in the late-stage epithelial ovarian carcinoma, indicating that PPARγ contributes significantly to the onset and progression of ovarian cancer [33]. Because the levels of PPARγ and the PPARγ coactivator, PGC-1α, are always linked to clinical outcome in patients with a variety of human cancers [12][13][14], it is reasonable to suspect that PGC-1α may also play a pivotal role in the pathogenic development of epithelial ovarian cancer.…”

“…Given that activation of PPARγ by its ligands can induce apoptosis in cancer and that PGC-1α also powerfully coactivates PPARγ, we speculate that there may be a potential relationship between PGC-1α and PPARγ in cancer development. A recent study has shown that the expression of PPARγ is indeed enhanced in epithelial ovarian carcinoma [23]; however, the role of PGC-1α in the pathogenesis of epithelial ovarian carcinoma remains to be addressed.…”