RB1 oncosuppressor gene over-expression inhibits tumor progression and induces melanogenesis in metastatic melanoma cells

Piera Valante, Antonella Melchiori, Marco G. Paggi, Lucia Masiello, Domenico Ribatti, Leonardo Santi, Rei Takahashi, Adriana Albini, Douglas M. Noonan

Research output: Contribution to journalArticle

Abstract

The retinoblastoma gene (RB1) is frequently deleted or mutated in many tumor types and in all cases of retinoblastoma. Apart from its role in regulation of the cell cycle, the RB1 gene product (p110(RB1)) appears to be involved in control of differentiation. Malignant metastatic cells show many properties of poorly differentiated cells, and are highly invasive in vitro and in vivo, We have transfected the human RB1 cDNA in an expression vector under the control of the β-actin promoter into B16F10 murine melanoma cells. These cells highly overexpress RB1 mRNA and the p110(RB1) product, show reduced growth rate and increased melanogenesis in vitro. Vector control transfectants showed no alteration of invasiveness. The p110(RB1) over-expressing cells also had a reduced capacity to migrate and invade through an artificial basement membrane, key characteristics of metastatic cells. When injected into nude mice, the p110(RB1) over-expressing cells showed reduced tumor growth and reduced metastatic potential, The few metastasis observed were predominantly melanotic. These data indicate that RB1 gene expression is involved in melanoma cell differentiation and plays a role in downregulation of migration, invasion and metastatic potential of these cells.

Original languageEnglish
Pages (from-to)1169-1178
Number of pages10
JournalOncogene
Volume13
Issue number6
Publication statusPublished - 1996

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Keywords

  • Invasion
  • Melanin
  • Melanoma
  • Retinoblastoma
  • Tumor progression

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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