Retention of these introns may have been responsible for the lack of dystrophin expression by CRL-2061 cells, thereby abolishing the tumor suppressor activity of dystrophin.
The analysis of RNAseq studies revealed a median frequency of DMD genetic alterations of 3.4%, higher or similar to other well-known tumor suppressor genes.
These findings validate dystrophin as a tumor suppressor and likely anti-metastatic factor, suggesting that therapies in development for muscular dystrophies may also have relevance in the treatment of cancer.
To identify microRNAs (miRNA) involved in metastasis, the expression of 254 miRNAs was measured across the following cell lines using microarray analysis: MDA-MB-231 breast cancer cells, cells that grew as a tumor in the mammary fat pad of nude mice (TMD-231), metastatic disease to the lungs (LMD-231), bone (BMD-231) and adrenal gland (ADMD-231).
Using a functional screening approach, we found that UTRN (which encodes utrophin, a dystrophin-related protein) at 6q24, when expressed in an antisense orientation, induced cellular transformation, consistent with a tumor suppressor role.
We performed typing of HPV-DNA using a polymerase chain reaction (PCR), and amplified the Duchenne muscular dystrophy (DMD) genes simultaneously, to investigate the tumor DNA state.
Tumors in the subcutaneous tissue and peritoneum induced desmoplastic stroma (%St = 22.7%, 19.5%, respectively) and contained BMD-VE (%BMD-VE = 21.6%, 16.5% respectively) and BMD-MF (%BMD-MF = 29.6%, 24.5%, respectively), but weak stromal induction without recruitment of BMD-VE or -MF was observed in the tumors at of the liver, spleen and lung (%St = 9.7%, 9.1%, 5.4%, respectively). cDNA microarray analysis identified the 29 genes that expression was especially up- or down-regulated in the cell line that induced an abundant stromal reaction.