Identification of new genes related to the myogenic differentiation arrest of human rhabdomyosarcoma cells

Annalisa Astolfi, Carla De Giovanni, Lorena Landuzzi, Giordano Nicoletti, Cinzia Ricci, Stefania Croci, Luciano Scopece, Patrizia Nanni, Pier Luigi Lollini

Research output: Contribution to journalArticle

Abstract

Rhabdomyosarcoma is a soft tissue tumor committed to the myogenic lineage but arrested prior to terminal differentiation. To identify new genes implicated in the block in myogenic differentiation of rhabdomyosarcoma cells and those responsible for their proceeding along the myogenic pathway we used cDNA microarrays to compare gene expression profiles of two clones of the human embryonal rhabdomyosarcoma cell line RD with different myogenic potentials: RD/12, which is unable to differentiate, and RD/18, which shows elements able to terminally differentiate, as defined by the expression of myosin heavy chain (up to 50% of the population) and the formation of multinucleated myotube-like structures. We identified 80 genes differentially expressed by the two clones. Differentiating RD/18 cells overexpressed the myogenic transcription factor myogenin along with known myogenic markers; myogenin transfection into undifferentiated RD/12 cells was able to revert the phenotype giving rise to 94% of clones displaying a differentiated morphology. RD/18 cells also expressed several genes not known to be expressed in rhabdomyosarcoma or muscle cells, such as pigment-epithelium derived factor and endothelin-3. Poorly differentiated RD/12 cells, along with genes related to mesenchymal lineage or early myogenic commitment, also expressed genes not previously known to be related to the differentiation block of human rhabdomyosarcoma, such as monocyte chemotactic protein-1, connective tissue growth factor and insulin-like growth factor binding protein-5. Differential expression of these genes in a time course of differentiation suggested their potential roles as either new myogenic markers or repressors of differentiation. These results identify a cluster of new genes related to the aberrant myogenic differentiation program of human rhabdomyosarcoma cells.

Original languageEnglish
Pages (from-to)139-149
Number of pages11
JournalGene
Volume274
Issue number1-2
DOIs
Publication statusPublished - Aug 22 2001

Keywords

  • CDNA microarray
  • Myogenic differentiation
  • Reverse transcription-polymerase chain reaction
  • Rhabdomyosarcoma

ASJC Scopus subject areas

  • Genetics

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    Astolfi, A., De Giovanni, C., Landuzzi, L., Nicoletti, G., Ricci, C., Croci, S., Scopece, L., Nanni, P., & Lollini, P. L. (2001). Identification of new genes related to the myogenic differentiation arrest of human rhabdomyosarcoma cells. Gene, 274(1-2), 139-149. https://doi.org/10.1016/S0378-1119(01)00619-9