Novel candidate genes of thyroid tumourigenesis identified in Trk-T1 transgenic mice

Abstract

For an identification of novel candidate genes in thyroid tumourigenesis, we have investigated gene copy number changes in a Trk-T1 transgenic mouse model of thyroid neoplasia. For this aim, 30 thyroid tumours from Trk-T1 transgenics were investigated by comparative genomic hybridisation. Recurrent gene copy number alterations were identified and genes located in the altered chromosomal regions were analysed by Gene Ontology term enrichment analysis in order to reveal gene functions potentially associated with thyroid tumourigenesis. In thyroid neoplasms from Trk-T1 mice, a recurrent gain on chromosomal bands 1C4-E2.3 (10.0% of cases), and losses on 3H1-H3 (13.3%), 4D2.3-E2 (43.3%) and 14E4-E5 (6.7%) were identified. The genes Twist2, Ptma, Pde6d, Bmpr1b, Pdlim5, Unc5c, Srm, Trp73, Ythdf2, Taf12 and Slitrk5 are located in these chromosomal bands. Copy number changes of these genes were studied by fluorescence in situ hybridisation on 30 human papillary thyroid carcinoma (PTC) samples and altered gene expression was studied by qRT-PCR analyses in 67 human PTC. Copy number gains were detected in 83% of cases for TWIST2 and in 100% of cases for PTMA and PDE6D. DNA losses of SLITRK1 and SLITRK5 were observed in 21% of cases and of SLITRK6 in 16% of cases. Gene expression was significantly up-regulated for UNC5C and TP73 and significantly down-regulated for SLITRK5 in tumours compared with normal tissue. In conclusion, a global genomic copy number analysis of thyroid tumours from Trk-T1 transgenic mice revealed a number of novel gene alterations in thyroid tumourigenesis that are also prevalent in human PTCs.

High expression of metadherin correlates with malignant pathological features and poor prognostic significance in papillary thyroid carcinoma

“…TRK‐T1 is a fusion protein composed of the carboxyl terminal tyrosine kinase domain of NTRK1 and the amino terminal portion of TPR, TRK‐T1 fusion protein is enough to cause the occurrence of PTC . In TRK‐T1 fusion protein transferred thyroid mouse tumour model, TRK‐T1 could alter gene expression and promote cancer progression . In our results, high MTDH expression was found in PTC.…”

High expression of PDLIM5 facilitates cell tumorigenesis and migration by maintaining AMPK activation in prostate cancer

“…Besides, PDLIM5 was considered necessary in cell migration by forming lamellipodia, and phosphorylation inactivation of PDLIM5 was reported to weaken the cell metastasis capacity by inactivating RAC1 [ 10 ]. According to recent studies, PDLIM5 may participate in the progression of many types of cancer including thyroid cancer [ 11 ], lung cancer [ 12 ], breast cancer [ 13 ] and gastric cancer [ 14 ]. Koutros et al [ 15 ] reported that PDLIM5 mRNA was overexpressed in PCa tissues by using gene chip detection.…”

An Overview of the Cytoskeleton-Associated Role of PDLIM5

“…As an actin adaptor protein, PDLIM5 is not only involved in cytoskeletal tissue, cellular processes, and organ development, but is also considered to play roles in tumorigenesis and development (Eeckhoute, 2006;Edlund et al, 2012;Heiliger et al, 2012;Li et al, 2015). PDLIM5 is expressed in many cancer cell lines.…”

“…Dysfunction of the proteins of the PDZ-LIM family is known to affect the maintenance of organ function and weaken the invasion ability and metastatic potential of cancer cells (Bagheri-Yarmand et al, 2006;Tanaka-Okamoto et al, 2009). According to recent studies, PDLIM5 may be involved in the progression of multiple tumor types (Eeckhoute, 2006;Edlund et al, 2012;Heiliger et al, 2012;Li et al, 2015). The important role of PDLIM5 in various organizational systems have led to a deeper understanding of its physiological function.…”