Araştırma Çıktıları
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Item Endogenous c-Jun N-terminal kinase (JNK) activity marks the boundary between normal and malignant granulosa cells(NATURE PUBLISHING GROUP, 2018-01-01) Bildik, Gamze; Akin, Nazli; Senbabaoglu, Filiz; Esmalian, Yashar; Sahin, Gizem Nur; Urman, Defne; Karahuseyinoglu, Sercin; Ince, Umit; Palaoglu, Erhan; Taskiran, Cagatay; Arvas, Macit; Guzel, Yilmaz; Yakin, Kayhan; Oktem, OzgurGranulosa cell tumor of the ovary (GCT) is a very rare tumor, accounting for only 2\% of all ovarian tumors. It originates from sex cords in the ovary and can be divided into adult (95\%) and juvenile (5\%) types based on histologic findings. To date, no clear etiologic process has been identified other than a missense point mutation in the FOXL2 gene. Our previous works showed that c-Jun N-terminal kinase (JNK) pathway plays critical role in cell cycle progression and mitosis of normal and immortalized granulosa cells and follicle growth in rodent ovaries. These findings led us to investigate the role of JNK pathway in the granulosa cell tumor of the ovary. We used two different GCT cell lines (COV434 and KGN) and fresh GCT samples of adult and juvenile types obtained from the patients during surgery. We have discovered that endogenous kinase activity of JNK is markedly enhanced in the GCT samples and cell lines, whereas it was almost undetectable in mitotic non-malignant human granulosa cells. The inhibition of JNK pathway in GCT cell lines with two different pharmacologic inhibitors (SP600125 and AS601245) or siRNA resulted in a dose-dependent reduction in in vitro cell growth, increased apoptosis and diminished estradiol and AMH productions. JNK inhibition was also associated with a decrease in the number of cells positive for mitosis marker phospho-histone H3(Ser) 10 in the asynchronous cells