Pos sibly, GILZ may directly control the transcriptional activ ity of cyclin D1 as already demonstrated for other the molecules. Conclusion Few studies have identified particular molecules and their roles in the molecular mechanisms of tumor progression in EOC. Here, we report a previously unsuspected and important role for GILZ in the control of tumor cell pro liferation in EOC. Our findings were supported by parallel and complementary data from tumor specimens and work with the BG 1 cellular model. They demonstrate that, in EOC, GILZ increases tumor cell proliferation, acti vates AKT, down regulates p21 and promotes cyclin D1 expression. all these molecules are involved in the pro gression of malignant tumors and their deregulations are often associated to poor clinical outcome.

These findings highlight GILZ as a potential key molecule in EOC. Materials and methods Tissue samples Approval was obtained from the ethics commission of the Antoine B��cl��re Hospital for all analy ses of tumor material Inhibitors,Modulators,Libraries from clinical samples and from archival Inhibitors,Modulators,Libraries material from patients with a diagnosis of inva sive ovarian carcinoma. Immunohistochemical examina tion of GILZ, phosphorylated protein kinase B/AKT and Ki 67 proliferation index was performed retro spectively on tissue specimens of primary invasive ovarian carcinomas taken for routine diagnostic and therapeutic purposes from 50 patients who were treated surgically fol lowing a diagnosis of ovarian tumor at Antoine B��cl��re Hospital between 1998 and 2007. Clinical and patholog ical characteristics of the patients are detailed in Table 2.

None of the patients had received neo adjuvant chemo therapy before surgery. Clinical stage was assigned accord ing to the International Federation of Gynecology and Obstetrics staging system . histological subtypes and Inhibitors,Modulators,Libraries grades were assigned according to the criteria of the World Health Organization classification. Immunohistochemistry Inhibitors,Modulators,Libraries We tested for GILZ, Ki 67 and p AKT in EOC samples. Par affin embedded tissue sections were cut from representa tive blocks of tumor biopsies and probed with the following antibodies by the avidin biotin peroxidase Inhibitors,Modulators,Libraries method GILZ polyclo nal antibody, Ki 67 monoclonal Ab and phospho AKT Ab which recognizes only the phosphorylated form of AKT. Antigens were unmasked by incubation in 10 mmol/L sodium citrate buffer and heating at 90 C using a microwave oven.

Tissues were counterstained with hematoxylin. Neg ative controls were done without the primary Ab. Immu nochemical staining was simultaneously interpreted by two independent investigators without knowledge of the patients clinicopathological outcome. selleck chem Tofacitinib Immunostaining for GILZ and for Ki 67 were scored on a seven tiered scale as follows negative, 1, 2 or 3 combined with the per centage of positive cells scored as 0, 1, 2, 3, 4 as previously reported.