Open Access Research article

A systems analysis of the chemosensitivity of breast cancer cells to the polyamine analogue PG-11047

Wen-Lin Kuo1*, Debopriya Das1, Safiyyah Ziyad1, Sanchita Bhattacharya1, William J Gibb1, Laura M Heiser1, Anguraj Sadanandam1, Gerald V Fontenay1, Zhi Hu2, Nicholas J Wang1, Nora Bayani1, Heidi S Feiler1, Richard M Neve1, Andrew J Wyrobek1, Paul T Spellman1, Laurence J Marton3 and Joe W Gray12

Author affiliations

1 Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA

2 Comprehensive Cancer Center, University of California, San Francisco, California, USA

3 Progen Pharmaceuticals, Redwood City, California, USA

For all author emails, please log on.

Citation and License

BMC Medicine 2009, 7:77  doi:10.1186/1741-7015-7-77

Published: 14 December 2009



Polyamines regulate important cellular functions and polyamine dysregulation frequently occurs in cancer. The objective of this study was to use a systems approach to study the relative effects of PG-11047, a polyamine analogue, across breast cancer cells derived from different patients and to identify genetic markers associated with differential cytotoxicity.


A panel of 48 breast cell lines that mirror many transcriptional and genomic features present in primary human breast tumours were used to study the antiproliferative activity of PG-11047. Sensitive cell lines were further examined for cell cycle distribution and apoptotic response. Cell line responses, quantified by the GI50 (dose required for 50% relative growth inhibition) were correlated with the omic profiles of the cell lines to identify markers that predict response and cellular functions associated with drug sensitivity.


The concentrations of PG-11047 needed to inhibit growth of members of the panel of breast cell lines varied over a wide range, with basal-like cell lines being inhibited at lower concentrations than the luminal cell lines. Sensitive cell lines showed a significant decrease in S phase fraction at doses that produced little apoptosis. Correlation of the GI50 values with the omic profiles of the cell lines identified genomic, transcriptional and proteomic variables associated with response.


A 13-gene transcriptional marker set was developed as a predictor of response to PG-11047 that warrants clinical evaluation. Analyses of the pathways, networks and genes associated with response to PG-11047 suggest that response may be influenced by interferon signalling and differential inhibition of aspects of motility and epithelial to mesenchymal transition.

See the related commentary by Benes and Settleman: webcite