Down-regulation of Lysyl Oxidase-induced Tumorigenic Transformation in NRK-49F Cells Characterized by Constitutive Activation of Ras Proto-oncogene

Monia Giampuzzi, Gerardo Botti, Michele Cilli, Rosanna Gusmano, Agnès Borel, Pascal Sommer, Armando Di Donato

Research output: Contribution to journalArticle

Abstract

Several investigations have suggested a putative tumor suppressor role for lysyl oxidase because it is down-regulated in many human and oncogene-induced tumors. To address this issue we down-regulated the enzyme in normal rat kidney fibroblasts by stable transfection of its cDNA in an antisense orientation. The selected clones revealed an absence of lysyl oxidase and dramatic phenotypic changes, interpretable as signs of transformation. The antisense lysyl oxidase clones showed, indeed, loose attachment to the plate and anchorage-independent growth and were highly tumorigenic in nude mice. Moreover, we found an impaired response of the PDGF and IGF-1 receptors to their ligands. In particular, the transformed cells showed a down-regulation of both PDGF receptors and expressed the 105-kDa isoform of the IGF-1β receptor, which was not present in the normal control cells. The lack of response to PDGF-BB has been described as a feature of many ras-transformed phenotypes. Therefore, we looked at the status of the p21 ras. Indeed, we found a significantly higher level of active p21 ras both during steady-state growth and prolonged starvation. Our data reveal new evidence for a tumor suppressor activity of lysyl oxidase, highlighting its particular role in controlling Ras activation and growth factor dependence.

Original languageEnglish
Pages (from-to)29226-29232
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number31
DOIs
Publication statusPublished - Aug 3 2001

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Neoplastic Cell Transformation
Protein-Lysine 6-Oxidase
ras Genes
Proto-Oncogenes
Down-Regulation
Chemical activation
Proto-Oncogene Proteins p21(ras)
Tumors
IGF Type 1 Receptor
Clone Cells
Platelet-Derived Growth Factor Receptors
Neoplasms
Fibroblasts
Growth
Starvation
Oncogenes
Nude Mice
Transfection
Rats
Intercellular Signaling Peptides and Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Down-regulation of Lysyl Oxidase-induced Tumorigenic Transformation in NRK-49F Cells Characterized by Constitutive Activation of Ras Proto-oncogene. / Giampuzzi, Monia; Botti, Gerardo; Cilli, Michele; Gusmano, Rosanna; Borel, Agnès; Sommer, Pascal; Di Donato, Armando.

In: Journal of Biological Chemistry, Vol. 276, No. 31, 03.08.2001, p. 29226-29232.

Research output: Contribution to journalArticle

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