HMGA2 expression in a canine model of prostate cancer

Winkler, Susanne; Escobar, Hugo Murua; Meyer, Britta; Simón, Daniela; Eberle, N.; Baumgärtner, Wolfgang; Loeschke, Siegfried; Nolte, Ingo; Bullerdiek, Jörn

doi:10.1016/j.cancergencyto.2007.06.008

Cited by 20 publications

(22 citation statements)

References 18 publications

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“…HMGA2 standard curve sequence and amplification primers were based on a custom canine assay 91 and adjusted to the feline sequence. The feline HMGA2 sequence was obtained by aligning the human exon 2, 3 and 4 sequences (NM_001300918.1) against cat chromosome B4.…”

Section: Methodsmentioning

confidence: 99%

TiHo-0906: a new feline mammary cancer cell line with molecular, morphological, and immunocytological characteristics of epithelial to mesenchymal transition

Granados-Soler

Junginger

Hewicker‐Trautwein

et al. 2018

Sci Rep

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Feline mammary carcinomas (FMCs) with anaplastic and malignant spindle cells histologically resemble the human metaplastic breast carcinoma (hMBC), spindle-cell subtype. hMBCs display epithelial-to-mesenchymal transition (EMT) characteristics. Herein we report the establishment and characterization of a cell line (TiHoCMglAdcar0906; TiHo-0906) exhibiting EMT-like properties derived from an FMC with anaplastic and malignant spindle cells. Copy-number variations (CNVs) by next-generation sequencing and immunohistochemical characteristics of the cell line and the tumour were compared. The absolute qPCR expression of EMT-related markers HMGA2 and CD44 was determined. The growth, migration, and sensitivity to doxorubicin were assessed. TiHo-0906 CNVs affect several genomic regions harbouring known EMT-, breast cancer-, and hMBCs-associated genes as AKT1, GATA3, CCND2, CDK4, ZEB1, KRAS, HMGA2, ESRP1, MTDH, YWHAZ, and MYC. Most of them were located in amplified regions of feline chromosomes (FCAs) B4 and F2. TiHo-0906 cells displayed an epithelial/mesenchymal phenotype, and high HMGA2 and CD44 expression. Growth and migration remained comparable during subculturing. Low-passaged cells were two-fold more resistant to doxorubicin than high-passaged cells (IC50: 99.97 nM, and 41.22 nM, respectively). The TiHo-0906 cell line was derived from a poorly differentiated cellular subpopulation of the tumour consistently displaying EMT traits. The cell line presents excellent opportunities for studying EMT on FMCs.

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Section: Methodsmentioning

confidence: 99%

TiHo-0906: a new feline mammary cancer cell line with molecular, morphological, and immunocytological characteristics of epithelial to mesenchymal transition

Granados-Soler

Junginger

Hewicker‐Trautwein

et al. 2018

Sci Rep

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“…Similar to HMGA1 , an upregulation of HMGA2 was reported in human lung and breast cancers [75, 76] as well as in a subset of canine PCs [77]. Furthermore, HMGA2 was recently described to modify gene expression not only as protein but as well as a competing endogenous RNA (ceRNA) by acting as a decoy for mature let-7 miRNAs [78].…”

Section: Hmga2mentioning

confidence: 99%

Role of miRNALet-7and Its Major Targets in Prostate Cancer

Wagner

Ngezahayo

Escobar

et al. 2014

BioMed Research International

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Prostate cancer is worldwide the sixth leading cause of cancer related death in men thus early detection and successful treatment are still of major interest. The commonly performed screening of the prostate-specific antigen (PSA) is controversially discussed, as in many patients the prostate-specific antigen levels are chronically elevated in the absence of cancer. Due to the unsatisfying efficiency of available prostate cancer screening markers and the current treatment outcome of the aggressive hormone refractory prostate cancer, the evaluation of novel molecular markers and targets is considered an issue of high importance. MicroRNAs are relatively stable in body fluids orchestrating simultaneously the expression of many genes. These molecules are currently discussed to bear a greater diagnostic potential than protein-coding genes, being additionally promising therapeutic drugs and/or targets. Herein we review the potential impact of the microRNA let-7 family on prostate cancer and show how deregulation of several of its target genes could influence the cellular equilibrium in the prostate gland, promoting cancer development as they do in a variety of other human malignant neoplasias.

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“…Herein, the analysis of a subset of different canine prostate tissue samples clearly showed that expression of HMGA2 increases significantly in correlation to the malign grade of the tissue samples [17]. Furthermore, HMGA2 was found to serve as a potential differentiation marker of canine malignant T- and B-cell lymphoma [18] and to be strongly upregulated in canine oral squamous cell carcinoma (unpublished data).…”

Section: Introductionmentioning

confidence: 84%

“…In this context the High-Mobility-Group Protein A2 (HMGA2) was recently found to serve potentially as a prognostic marker for canine prostatic neoplasias [17]. Herein, the analysis of a subset of different canine prostate tissue samples clearly showed that expression of HMGA2 increases significantly in correlation to the malign grade of the tissue samples [17].…”

Section: Introductionmentioning

confidence: 95%

Generation and Characterisation of a Canine EGFP-HMGA2 Prostate Cancer In Vitro Model

et al. 2014

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The architectural transcription factor HMGA2 is abundantly expressed during embryonic development. In several malignant neoplasias including prostate cancer, high re-expression of HMGA2 is correlated with malignancy and poor prognosis. The let-7 miRNA family is described to regulate HMGA2 negatively. The balance of let-7 and HMGA2 is discussed to play a major role in tumour aetiology. To further analyse the role of HMGA2 in prostate cancer a stable and highly reproducible in vitro model system is precondition. Herein we established a canine CT1258-EGFP-HMGA2 prostate cancer cell line stably overexpressing HMGA2 linked to EGFP and in addition the reference cell line CT1258-EGFP expressing solely EGFP to exclude EGFP-induced effects. Both recombinant cell lines were characterised by fluorescence microscopy, flow cytometry and immunocytochemistry. The proliferative effect of ectopically overexpressed HMGA2 was determined via BrdU assays. Comparative karyotyping of the derived and the initial CT1258 cell lines was performed to analyse chromosome consistency. The impact of the ectopic HMGA2 expression on its regulator let-7a was analysed by quantitative real-time PCR. Fluorescence microscopy and immunocytochemistry detected successful expression of the EGFP-HMGA2 fusion protein exclusively accumulating in the nucleus. Gene expression analyses confirmed HMGA2 overexpression in CT1258-EGFP-HMGA2 in comparison to CT1258-EGFP and native cells. Significantly higher let-7a expression levels were found in CT1258-EGFP-HMGA2 and CT1258-EGFP. The BrdU assays detected an increased proliferation of CT1258-HMGA2-EGFP cells compared to CT1258-EGFP and native CT1258. The cytogenetic analyses of CT1258-EGFP and CT1258-EGFP-HMGA2 resulted in a comparable hyperdiploid karyotype as described for native CT1258 cells. To further investigate the impact of recombinant overexpressed HMGA2 on CT1258 cells, other selected targets described to underlie HMGA2 regulation were screened in addition. The new fluorescent CT1258-EGFP-HMGA2 cell line is a stable tool enabling in vitro and in vivo analyses of the HMGA2-mediated effects on cells and the development and pathogenesis of prostate cancer.

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HMGA2 expression in a canine model of prostate cancer

Cited by 20 publications

References 18 publications

TiHo-0906: a new feline mammary cancer cell line with molecular, morphological, and immunocytological characteristics of epithelial to mesenchymal transition

TiHo-0906: a new feline mammary cancer cell line with molecular, morphological, and immunocytological characteristics of epithelial to mesenchymal transition

Role of miRNALet-7and Its Major Targets in Prostate Cancer

Generation and Characterisation of a Canine EGFP-HMGA2 Prostate Cancer In Vitro Model

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