Polyamines induce malignant transformation in cultured NIH 3T3 fibroblasts

Amalia Tabib, Uriel Bachrach*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


Previous studies have demonstrated that polyamines accumulate in cancer cells and that overproduction of ornithine decarboxylase (ODC), which catalyzes polyamine synthesis, elicits the acquisition of the transformed phenotype. However, it was not clear whether the overexpression of ODC and the accumulation of polyamines are only innocent by-products of the transformation process. In this study we demonstrate that polyamines as such, may play a crucial role in malignant transformation. The system used consisted of NIH 3T3 fibroblasts transfected with a construct (pATMras) in which Ha-ras was under the transcriptional control of the mouse mammary tumor virus long terminal repeat (MMTV-LTR) promoter (MMTVras cells). Dexamethasone, which activates the promoter, triggered phenotypic transformation. This was accompanied by an increase in ODC activity and polyamine accumulation. Cells, thus transformed, grew in soft agar and formed typical loci. α-Difluoromethylornithine (DFMO), which blocks polyamine synthesis, inhibited the dexamethasone-enhanced transformation. This inhibition was reversed by polyamines. Polyamines caused transformation of MMTVras cells in the absence of dexamethasone. Under these conditions, cells became anchorage independent. This phenomenon is not explained by the leakiness of ras, since normal, immortalized NIH 3T3 fibroblasts, also grew in soft agar in the presence of polyamines. Taken together, these observations suggest that polyamines may stimulate malignant transformation of immortalized cells, in cooperation with other factors, such as oncogenes or genetic defects.

Original languageAmerican English
Pages (from-to)135-146
Number of pages12
JournalInternational Journal of Biochemistry and Cell Biology
Issue number1
StatePublished - 19 Mar 1998

Bibliographical note

Funding Information:
This work was supported by a grant from the Fritz Foundation. The generous support by the Joseph H. Sciaky Memorial Foundation is greatly appreciated.


  • Dexamethasone
  • Fibroblasts
  • Polyamines
  • Soft agar
  • Transformation


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