Treatment of a limited number of human breast cancer cell lines in cul ture with PG 11047 has been reported to inhibit cell growth and or induce cell death. To better deline ate the response of breast cancer cells to PG 11047, we studied the antiproliferative activity of this drug in a panel of 48 breast cell despite lines that mirror many transcriptional and genomic features present in primary human breast tumours. The initial characterization of this panel shows that the cell lines are comprised of three subtypes designated basal A, basal B and luminal. The basal A subtype corresponds most closely to tumours designated as basal like by expression profiling while the basal B subtype corre sponds most closely to tumours designated as claudin low.

Inhibitors,Modulators,Libraries The basal A and basal B subtypes will be referred to as basal and claudin low, respectively, in the following text. Our studies show that basal subtype breast cancer cell lines are most sensitive to treatment with PG 11047 Inhibitors,Modulators,Libraries based on the dose required to inhibit 50% relative growth. Correlations between cell line responses quanti fied by the GI50 and the transcriptional and genomic char acteristics of these cell lines identified a set of 250 genes that are associated with response. A signature comprised of 13 of these genes is Inhibitors,Modulators,Libraries proposed as a predictor of response to PG 11047 treatment in breast tumours. Methods Breast cancer cell lines Breast cancer cell lines were obtained from the American Type Culture Collection and from collections developed in the laboratories of Drs Steve Ethier and Adi Gazdar.

Forty of the cell lines were charac terized in great detail by Neve et al, eight were acquired recently and characterized in similar fashion for subtype classification. The recurrent genome copy number abnormal ities in the collection of cell lines Inhibitors,Modulators,Libraries was similar to those in primary tumours, while hierarchical analysis of the tran scriptional features of the cell lines defined three clusters designated luminal, basal and claudin low. Cell growth inhibition assay and data analysis Cells were plated at proper density in 96 well plates, so that they remained in logarithmic growth at the time of assay. The cells were allowed to attach overnight before being exposed to the polyamine analogue PG 11047 for 72 h. Inhibitors,Modulators,Libraries PG 11047 6,7 dehydrospermine tetrahydrochloride, previously known as SL 11047 and CGC 11047 was obtained from Progen Pharmaceuticals and a stock solution of 100 mM was prepared in sterile water.

For the dose response study, a set of nine doses in 1 5 serial dilution were added in triplicate wells. Adenosine triphosphate content was measured as an estimate of relative cell number using the CellTiter Glo Luminescent Cell Viability Erlotinib HCl Assay, with slight modification form manufacturers pro tocol, at day 0 and day 3 of drug exposure.