Differential expression of invasion promoting genes in childhood rhabdomyosarcoma

Abstract

Abstract. expression profiling of tumor tissue allows a systematic search for targeted therapies and offers relevant prognostic information. Molecular studies on rhabdomyosarcoma (RMS) revealed a more differentiated classification than the histological subgrouping into embryonal (rMe) and alveolar (RMA) rhabdomyosarcoma, and reflected the chromosomal aberrations found in rMS. We addressed biological processes like cell migration and emerging drug resistance by expression profiling to identify mechanisms of metastasic invasion and differential response to chemotherapy in rMS. gene expression analysis was performed in 19 rMS samples using the affymetrix u133 Plus2 array. Validation of target genes was performed by qrt-Pcr. Data were analyzed using Pathway analysis software. involvement of these genes in invasion processes was evaluated in knock-down experiments using specific interference rna and Matrigel tM invasion assay. in rMa tissues 211 of 534 genes were overexpressed, in rMe tissues 323 genes were overexpressed. Pathway analysis software identified a group of genes involved in cell growth, morphology and motility. in patients with distant metastases especially transcription factors such as foXf1 and lMo4 showed a high expression, which were described as determinants of tumor cell migration. Down-regulation of these factors inhibited the invasion of rMS cells >10-fold. Microarray technology is a powerful method not only to classify rMS samples, but also to identify major regulatory processes. functional evaluation of lMo4 and foXf1 identified targets of a molecular network for preventing metastatic invasion in rMS.

FoxF1 and FoxF2 transcription factors synergistically promote rhabdomyosarcoma carcinogenesis by repressing transcription of p21Cip1 CDK inhibitor

“…Based on gene expression arrays, there is growing evidence that RMS is a heterogeneous disease with multiple molecular subtypes (8-10). Interestingly, analysis of clinical RMS samples demonstrated that Forkhead Box F1 (FoxF1) transcription factor is one of the consistently upregulated genes in translocation-positive alveolar RMS, indicating its potential role in the aggressiveness of this disease (8-11). …”

Lethal lung hypoplasia and vascular defects in mice with conditionalFoxf1overexpression

“…FOXF1 has also been reported to be epigenetically inactivated in breast and colorectal cancers (Lo et al, 2010; Mitchell et al, 2014) and overexpressed in Patched-associated tumors, including basal cell carcinoma, medulloblastoma, and rhabdomyosarcoma (Wendling et al, 2008a; Armeanu-Ebinger et al, 2011). FOXF1 overexpression was found in lung fibroblasts from patients with idiopathic pulmonary fibrosis (Melboucy-Belkhir et al, 2014).…”

Differential expression of miRNAs in rhabdomyosarcoma and malignant rhabdoid tumor

“…However, loss of E-cadherin expression can result from mechanisms other than ZEB1 or miR-9 Ã repression, as for instance chromosomal deletion and promoter hypermethylation [60][61][62][63]. Furthermore, other transcriptional repressors like SIP1 (ZEB2), Twist, Snail, and Slug with high expression in RMA [64] may suppress E-cadherin expression [65]. Therefore, even when repression by ZEB1 and miR-9 Ã is relieved, E-cadherin expression may remain blocked and cell migration characteristics remain constant.…”