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Pathways affected by Tamoxifen treatment inferred by human and rat expression data

Wednesday, September 12, 2018 — Poster Session II

3:30 p.m. – 5:00 p.m.
FAES Terrace
NCI
CANCER-40

Authors

  • HH YANG
  • HT LIU
  • R LUBET
  • MP LEE

Abstract

To explore potential of using the tamoxifen for breast cancer (BC) prevention, we used the rat model to evaluate the effect of the drug applied at different dosages based on the gene expression assay. The rats consisted of three groups: the control group, the two groups treated with 3.3ppm (mg of tamoxifen per g of diet) and 100ppm tamoxifen per day respectively. We compared each treatment group with the control to find the up or down regulated genes. At FDR=0.2, the number of differential expressed (DE) genes increased from 584 genes to 2267 genes when the dosage increased from 3.3ppm to 100ppm. The 3.3ppm treatment yielded less DE genes compared to the number of the DE genes affected by the 100ppm treatment, but 350 genes (Rat_Tam.vs.Ctrl) were shared by the two sets of the DE genes. Using the human Tamoxifen treatment dataset GSE6532 in GEO, we found 633 DE genes (GSE6532Tam.vs.Ctr) by comparing the treated (n=277) and untreated (n=237) patients. Using the human and rat homolog genes, we found 68 shared genes derived from 100ppm treatment and 11 genes from 3.3ppm treatment. 9 of the 11 genes regulated by the low dosage were also regulated by the high dosage. These genes included RAB5B, member RAS oncogene family, and PRKACB. By gene enrichment analysis (GSEA), we found several pathways including RAS Pathway, TGF Beta Signaling Pathway, DNA damage signalling and Cell Cycle pathways affected by the tamoxifen treatment. In METABRIC 420 patients had hormone treatment (HT) and compare their expression and that of 309 controls, we found 2616 differentially expressed genes at FDR=0.05. When this set of genes intersects with GSE6532Tam.vs.Ctr and Rat_Tam.vs.Ctrl), we obtained 4 genes XBP1 MON1B PLA2G6 NPEPL1. Our study gave evidence that the rat expression were regulated by tamoxifen even at low dosage.

Category: Cancer Biology