Dataset Information
The oncogene Gankyrin is expressed in testicular cancer and contributes to cisplatin sensitivity in embryonal carcinoma cells.
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ABSTRACT: Background
Testicular germ cell cancer (TGCC) develops from pre-malignant germ neoplasia in situ (GCNIS) cells. GCNIS originates from fetal gonocytes (POU5F1+/MAGE-A4-), which fail to differentiate to pre-spermatogonia (POU5F1-/MAGE-A4+) and undergo malignant transformation. Gankyrin is an oncogene which has been shown to prevent POU5F1 degradation and specifically interact with MAGE-A4 in hepatocellular carcinoma (HCC) cells. We aimed to investigate the role of Gankyrin in progression from gonocyte to pre-invasive GCNIS and subsequent invasive TGCC.Methods
We determined Gankyrin expression in human fetal testicular tissue (gestational weeks 9-20; n?=?38), human adult testicular tissue with active spermatogenesis (n?=?9), human testicular tissue with germ cell maturation delay (n?=?4), testicular tissue from patients with pre-invasive GCNIS (n?=?6), and invasive TGCC including seminoma (n?=?6) and teratoma (n?=?7). Functional analysis was performed in-vitro by siRNA knock-down of Gankyrin in the NTera2 cells (derived from embryonal carcinoma).Results
Germ cell expression of Gankyrin was restricted to a sub-population of prespermatogonia in human fetal testes. Nuclear Gankyrin was also expressed in GCNIS cells of childhood and adult pre-invasive TGCC patients, and in GCNIS from seminoma and non-seminoma patients. Cytoplasmic expression was observed in seminoma tumour cells and NTera2 cells. Gankyrin knock-down in NTera2 cells resulted in an increase in apoptosis mediated via the TP53 pathway, whilst POU5F1 expression was unaffected. Furthermore, Gankyrin knock-down in NTera2 cells increased cisplatin sensitivity with an increase in cell death (13%, p?ConclusionsThese results suggest that manipulation of Gankyrin expression may reduce the cisplatin dose required for the treatment of TGCC, with benefits in reducing dose-dependent side effects of chemotherapy. Further studies are required in order to assess the effects of modulating Gankyrin on GCNIS/TGCC using in vivo models.
SUBMITTER: Camacho-Moll ME
PROVIDER: S-EPMC6862764 | biostudies-literature | 2019 Nov
REPOSITORIES: biostudies-literature
Publications
The oncogene Gankyrin is expressed in testicular cancer and contributes to cisplatin sensitivity in embryonal carcinoma cells.
BMC cancer 20191119 1
<h4>Background</h4>Testicular germ cell cancer (TGCC) develops from pre-malignant germ neoplasia in situ (GCNIS) cells. GCNIS originates from fetal gonocytes (POU5F1<sup>+</sup>/MAGE-A4<sup>-</sup>), which fail to differentiate to pre-spermatogonia (POU5F1<sup>-</sup>/MAGE-A4<sup>+</sup>) and undergo malignant transformation. Gankyrin is an oncogene which has been shown to prevent POU5F1 degradation and specifically interact with MAGE-A4 in hepatocellular carcinoma (HCC) cells. We aimed to inves ...[more]
