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Introduction: Estrogen (E2) is pivotal to normal breast development and in initiation and progression of breast carcinoma. Despite identification of novel E2 targets in breast from SAGE and microarray (MA) generated gene expression data, differences in the adaptive mechanisms favoring proliferation in E2 responsive cancer cells remain unknown, more so in the context of normal breast (NB) cells. Objectives: to study the differential nature of two E2 responsive breast cell lines (E2 deprived), MCF7 and ZR75 from the publicly available SAGE and MA expression data using biocomputational tools. Data analysis: SAGE software extracted significant genes were also analyzed by Audic Claverie, Fisher and Chi2 statistical tests (IDEG6), yielding 230 (MCF7) and 134 (ZR75) genes (p≤0.05, MCF7/NB or ZR75/NB ≥ 5/≤ -5). DAVID tool annotated 133 (ZR75) and 227 (MCF7) genes. Classified genes included 32% (biological process P), 35% (molecular function F), and 32% (component C) leaving ∼ 68% (high) genes unclassified in both. However, GO term utilization (P, F, C) among the classified genes was comparable (P 32.3%, F 34.6%, C 32.3%-ZR75 and P 32.2%, F 32.6%, C 27.8%-MCF7). Pathway differences were also identified by GenMAPP tool. Further, SAGE dataset was compared with Affymetrix MA dataset for MCF7. Finding summary: The two cell lines differentially expressed 9 out of ∼ 75 common genes and 160 (MCF7) and 96 (ZR75) genes were specific. GenMAPP revealed the differences in proteosomal degradation pathways and utilization of energy pathways, such as glycolysis & gluconeogenesis and electron transport chain genes expressing proteins for complexes I, III, IV, V, MCF7 up-regulating more genes (Table 1). In contrast to MCF7, ZR75 down-regulated more immune response genes. Conclusions: while both E2 responsive cells can thrive under harsh E2 deprived conditions, ZR75 cells possess a greater capability of minimizing energy requirements, proteosomal degradation, and compromising immune responses, resembling the more aggressive ER negative breast cancer cells. In contrast, MCF7 cells highly utilize these pathways rendering them less aggressive. These differences can be exploited for specific targeting of hormone dependent breast cancer.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]