Ssion [39,40]. Our results indicate that around half of the BAY1217389MedChemExpress BAY1217389 tumors express
Ssion [39,40]. Our results indicate that around half of the tumors express the PDGFR, PDGFR and PDGFA, in both tumor and stroma as shown in Figure 1. We found no expression of the B ligand in tumor samples, which was surprising as 5 out of 8 cervical cancer cell lines expressed this ligand. In addition, both ligands have been found expressed in a number of other tumor types [9]. Whether this feature is unique to primary cervical cancer tumors merits further study. Interestingly 78 of the primary tumors express either the alpha or beta receptor. This elevated frequency of expression and co-expression highly suggest autocrine and paracrine functioning in cervical cancer tumors. This high frequency of expression and co-expression also occurred in the cervical cancer cell lines studied. It has been shown that the sole expression of PDGF receptors correlates with known adverse prognostic factors such as axillary lymph node metastases in breast cancer [28]. However, in this study we found no correlation between any combination of PDGF members expression with neither clinical characteristics of patients nor survival (data not shown). This observation does not exclude the possible prognostic significance of these receptors in cervical cancer. We alsostudied the mutational status of the PDGFR, based on the identification of activating gene mutations within a subset of GISTs that lacked KIT gene mutation, and where constitutive phosphorylation of PDGFR was observed, and the corresponding PDGFR isoforms demonstrated ligand-independent kinase activity [29]. These observations have profound PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28381880 implications for the treatment of solid tumors with imatinib, as some of these mutations confer either sensitivity or resistance to this tyrosine kinase inhibitor [41]. This can be explained on the lack of differences in the activation of downstream signaling intermediates between KIT-mutant and PDGFR-mutant tumors, suggesting that mutant PDGFR provides oncogenic signals that parallel those of mutant KIT [29]. Our sequence results indicate that the cervical cancer cell lines and primary tumors analyzed showed a number of intronic and exonic variations, most of them previously unreported, (Tables 2 and 3). The mutation G>A in codon 571 leading to a Glu>Lys substitution found in three of the cell lines has not been reported; however, the deletion/substitution SPDGHE566-571R (already reported) involves codon 571 which corresponds to the juxtamembrane domain of the protein. The significance of this change in regard to imatinib sensitivity is unknown [42] but this deletion increases PDGFR activation in the presence of PDGFA [29] suggesting that the mutation that we found, could affect the PDGFR functioning. In an attempt to study the possible effect of this mutation on the protein, we used the simulation program PolyPhen [43] to predict whether this mutation, found in the cell lines, is likely to have biological meaning. The results indicate that the G>A at codon 571 of exon 12 is “bening”. It is clear however, that this is only a theoretical approximation hence; the meaning of changes found must be investigated in experimental systems [44]. Besides, most of the intronic changes that we found are located in the proximity of the exon boundaries, and their possible meaning has to be studied. Regarding the samples from patients, we found the silent mutation at codon 824 already reported, in 10 out of 17 patients (59 ). In the normal cervical samples, we found that 6 out.

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