Background Testicular germ cell tumors (TGCTs) respond well to cisplatin-based chemotherapy and show a low incidence of attained resistance compared to most somatic tumors. genes showed that they participate in a variety of different and widely distributed functional groups and biochemical pathways. Database mining showed significant association of genes (n = 41) induced by cisplatin in our study, and genes previously reported to by indicated in differentiated TGCT cells. We recognized 37 p53-responsive genes that were modified after cisplatin exposure. We also recognized 40 target genes for two microRNAs, hsa-mir-372 and 373 that may interfere with p53 signaling in TGCTs. The tumor suppressor genes NEO1 and LATS2, and the estrogen receptor gene ESR1, all have binding sites for p53 and hsa-mir-372/373. NEO1 and LATS2 were down-regulated in TGCT cells following cisplatin exposure, while ESR1 was up-regulated in TGCT cells. Cisplatin-induced genes associated with terminal growth arrest through senescence were identified, indicating associations which were 1118807-13-8 supplier not previously explained for TGCT cells. Summary By linking our gene manifestation data to publicly available databases and literature, we provide a global pattern of cisplatin induced cellular response that is specific for testicular malignancy cell lines. We have recognized cisplatin-responsive practical classes and pathways, such as the Rabbit Polyclonal to MARK2 angiogenesis, Wnt, integrin, and cadherin signaling pathways. The recognition of differentially indicated genes with this study may contribute to a better understanding of the unusual level of sensitivity of TGCT to some DNA-damaging providers. Background Testicular germ cell tumors (TGCTs) are the most common tumors among young men. Fortunately, they respond well to cisplatin (Cis-Diamminedichloroplatinum (II) or CDDP)-centered chemotherapy and there is a low incidence of acquired resistance for TGCT compared to most somatic tumors. More than 80% of all TGCTs with metastatic disease are curable using cisplatin-based chemotherapy . TGCT are histologically classified as seminomas or non-seminomas, both originating from a common precursor known as carcinoma in situ (also known as intratubular germ cell neoplasia of the unclassified type) [2-4]. TGCT derived cell lines have often been used as model for studying cisplatin response [5,6]. The cause of their extreme level of sensitivity to chemotherapy seems 1118807-13-8 supplier to be multifactorial. TGCTs are “prone to apoptosis” and some studies possess reported high levels of the pro-apoptotic Bax protein and low levels of the anti-apoptotic Bcl-2 protein (high Bax:Bcl-2 percentage), and elevated wild-type p53 function [7-10]. You will find, however, conflicting reports on the part of the p53 status. The level of sensitivity toward cisplatin may also be an inherent home of primordial germ cells (PGCs) or gonocytes which are likely precursor cells for TGCTs . Besides cisplatin, 1118807-13-8 supplier TGCTs are highly sensitive also to additional chemotherapeutic medicines such as etoposide, ifosfamide, bleomycin, and vinblastine . Much like these providers, cisplatin is definitely a DNA-damaging drug; cisplatin binds to form both intra- and inter-strand cross-links, and is thought to exert its cytotoxic effects through irreversible binding with DNA. One would hence expect variance in DNA restoration capacities to be of importance for cell-type specific cisplatin sensitivity. Some studies possess explained a reduced ability of TGCT cells to repair cisplatin-induced DNA lesions, which is associated with a reduced manifestation level of several nucleotide excision restoration (NER) proteins [13,14]. Cisplatin-adducts are removed from DNA primarily by NER . In addition, It has been suggested that testis specific high-mobility group website proteins such as SRY (testis-determining element gene) may shield the cisplatin-induced DNA lesions from DNA restoration proteins [16,17]. We have previously reported on DNA restoration capacities in normal male germ cells. NER seems to be low in normal male germ cells compared to somatic cells , whereas foundation excision restoration (BER) of oxidative lesions appears to be.