VHL induces renal cell differentiation and growth arrest through integration of cell-cell and cell-extracellular matrix signaling

E. J. Davidowitz, A. R. Schoenfeld, Robert D. Burk

Research output: Contribution to journalArticle

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Abstract

Mutations in the von Hippel-Lindau (VHL) gene are involved in the family cancer syndrome for which it is named and the development of sporadic renal cell cancer (RCC). Reintroduction of VHL into RCC cells lacking functional VHL [VHL(-)] can suppress their growth in nude mice, but not under standard tissue culture conditions. To examine the hypothesis that the tumor suppressor function of VHL requires signaling through contact with extracellular matrix (ECM), 786-O VHL(-) RCC cells and isogenic sublines stably expressing VHL gene products [VHL(+)] were grown on ECMs. Cell-cell and cell-ECM signalings were required to elicit VHL-dependent differences in growth and differentiation. VHL(+) cells differentiated into organized epithelial sheets, whereas VHL(-) cells were branched and disorganized. VHL(+) cells grown to high density on collagen I underwent growth arrest, whereas VHL(-) cells continued to proliferate. Integrin levels were up-regulated in VHL(-) cells, and cell adhesion was down-regulated in VHL(+) cells during growth at high cell density. Hepatocyte nuclear factor 1α, a transcription factor and global activator of proximal tubule-specific genes in the nephron, was markedly up-regulated in VHL(+) cells grown at high cell density. These data indicate that VHL can induce renal cell differentiation and mediate growth arrest through integration of cell-cell and cell-ECM signals.

Original languageEnglish (US)
Pages (from-to)865-874
Number of pages10
JournalMolecular and Cellular Biology
Volume21
Issue number3
DOIs
StatePublished - 2001

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Extracellular Matrix
Cell Differentiation
Kidney
Growth
Renal Cell Carcinoma
Hepatocyte Nuclear Factor 1
Cell Count
Genes
Nephrons
Nude Mice
Cell Adhesion
Integrins
Neoplasms
Transcription Factors
Collagen

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

VHL induces renal cell differentiation and growth arrest through integration of cell-cell and cell-extracellular matrix signaling. / Davidowitz, E. J.; Schoenfeld, A. R.; Burk, Robert D.

In: Molecular and Cellular Biology, Vol. 21, No. 3, 2001, p. 865-874.

Research output: Contribution to journalArticle

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