At low nanomolar concentrations, BPA, TBBPA, and TCBPA decreased chemerin expression and secretion only in granulosa cell tumor COV434 cells by both peroxisome proliferator-activated receptor γ and estrogen receptor signaling pathways.
At low nanomolar concentrations, BPA, TBBPA, and TCBPA decreased chemerin expression and secretion only in granulosa cell tumor COV434 cells by both peroxisome proliferator-activated receptor γ and estrogen receptor signaling pathways.
In the present study, we demonstrated that the mRNA level of chemerin receptor is higher in a granulosa cell tumor cell line than in epithelial cancer cells, whereas chemerin expression and secretion were lower.
In the present study, we demonstrated that the mRNA level of chemerin receptor is higher in a granulosa cell tumor cell line than in epithelial cancer cells, whereas chemerin expression and secretion were lower.
We further investigated the molecular features of testicular tumors and determined the expression of beta-catenin (CTNNB1) known to be involved in testicular GrCT development.
The concomitant activation of CTNNB1 and KRAS in Sertoli cells also caused testicular granulosa cell tumors that showed gene expression patterns that partially overlapped those observed in GCTs of the ovary.
More recently, studies using loss- and gain-of-function transgenic mouse models demonstrated the requirement for Wnt4, Fzd4 and Ctnnb1, components of the WNT pathway, for normal folliculogenesis, luteogenesis and steroidogenesis, and showed that dysregulated WNT signaling can cause granulosa cell tumor development.
Aberrant granulosa cell-fate related to inactivated p53/Rb signaling contributes to granulosa cell tumors and to FOXL2 downregulation in the mouse ovary.
Adult-type granulosa cell tumors are molecularly characterized by a pathognomonic somatic missense point mutation 402C->G (C134W) in the transcription factor FOXL2.
Our study shows that half of granulosa theca cell tumors harbor the same FOXL2 mutation that characterizes adult granulosa cell tumors but there is no outcome evidence to guide whether mutation status should alter the classification of the tumor or the management of the patient.
FOXL2 ctDNA mutations were detected in the plasma of 12 of 33 AGCT patients (36%), with both primary (6 of 17, 35%) and recurrent (6 of 31, 19%) tumors.
The results of this case study indicated that although FOXL2 402C > G mutation determines the development of granulosa cell tumor, PMS2 mutation may be the initial driver of carcinogenesis.
We also undertook FOXL2 and DICER1 mutation analysis in these cases; a somatic missense mutation in codon C134W (402C→G) of FOXL2 gene has been demonstrated in the vast majority (>95%) of ovarian adult granulosa cell tumors and somatic DICER1 mutations are found in approximately 60% of ovarian Sertoli-Leydig cell tumors.
Identification and Validation of Differential Phosphorylation Sites of the Nuclear FOXL2 Protein as Potential Novel Biomarkers for Adult-Type Granulosa Cell Tumors.
FOXL2 immunoexpression has recently been found in sex cord stromal tumors of the ovary, including granulosa cell tumors, Sertoli-Leydig cell tumors, thecomas, and fibromas, but mutations have been identified mostly in adult granulosa cell tumors.
In the present study, we evaluated and compared apoptotic and antiproliferative activities of wild-type (WT) and mutant FOXL2 proteins found in BPES type I and II in human granulosa cell tumor-derived KGN cells.
Aberrant ovarian granulosa cell proliferation and apoptosis may lead to granulosa cell tumors (GCT), the pathogenesis of which involves transcription factors GATA4, FOXL2, and SMAD3.
To assess whether FOXL2p.C134W mutation may play a role in the development of human ovarian tumors in the Japanese, we investigated the FOXL2 codon 134 mutation and protein expression of inhibin-α, bone morphogenetic protein 2 (BMP2) and follistatin (FST) in Japanese patients with granulosa cell tumor (GCT) of the ovary and other ovarian tumors.