HOXB7 constitutively activates basic fibroblast growth factor in melanomas

Alessandra Carè, Anna Silvani, Ettore Meccia, Gianfranco Mattia, Antonella Stoppacciaro, Giorgio Parmiani, Cesare Peschle, Mario P. Colombo

Research output: Contribution to journalArticle

Abstract

Homeobox (HOX) genes control axial specification during mammalian development and also regulate skin morphogenesis. Although selected HOX genes are variably expressed in leukemias and kidney and colon cancer cell lines, their relationship with the neoplastic phenotype remains unclear. In both normal development and neoplastic transformation, HOX target genes are largely unknown. We investigated the expression and function of HOXB cluster genes in human melanoma. The HOXB7 gene was constitutively expressed in all 25 melanoma cell lines and analyzed under both normal and serum-starved conditions, as well as in in vivo primary and metastatic melanoma cells; conversely, HOXB7 was expressed in proliferating but not quiescent normal melanocytes. Treatment of melanoma cell lines with antisense oligomers targeting HOXB7 mRNA markedly inhibited cell proliferation and specifically abolished expression of basic fibroblast growth factor (bFGF) mRNA. Band shift and cotransfection experiments showed that HOXB7 directly transactivates the bFGF gene through one out of five putative homeodomain binding sites present in its promoter. These novel findings indicate a key role for constitutive HOXB7 expression in melanoma cell proliferation via bFGF. The results also raise the possibility that growth factor genes are critical HOX target genes in other developmental and/or neoplastic cell systems.

Original languageEnglish
Pages (from-to)4842-4851
Number of pages10
JournalMolecular and Cellular Biology
Volume16
Issue number9
Publication statusPublished - 1996

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

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    Carè, A., Silvani, A., Meccia, E., Mattia, G., Stoppacciaro, A., Parmiani, G., Peschle, C., & Colombo, M. P. (1996). HOXB7 constitutively activates basic fibroblast growth factor in melanomas. Molecular and Cellular Biology, 16(9), 4842-4851.