Comparative Proteomics Analysis of SKBR3 and MCF7 Breast Cancer Cell Lines Using Two Dimensional Electrophoresis: Ready to Build Postgenomics Capacity for OMICS R&D in Developing Countries?

Zahra      Mojtahedi; Nasrollah      Erfani; Abbas      Ghaderi

Abstract

Identifying novel molecular drug targets continues to be of prime interest in addressing the public health burden of breast cancer in both developed and developing countries alike. In this context, proteomics/pharmacoproteomics approaches offer a new dimension for personalized medicine. We have previously identified differentially expressed proteins with antigenic activity between SKBR3 (ER-, high HER2 expression) and MCF7 (ER+, low HER2 expression) breast cancer cell lines. The aims of the present study were (1) to develop an initial proteome based roadmap of differentially expressed proteins between the two cell lines using two-dimensional electrophoresis (2-DE), and (2) to compare them to those identified by other techniques. SKBR3 and MCF7 cell lysates were subjected to 2-DE and spots of interest were identified by MALDI-TOF/TOF MS. Upregulated proteins (≥2 fold and p<0.05) in MCF7 cells were cellular retinoic acid binding-protein-2, Hsp27, nucleophosmin, electron transfer flavoprotein-α, and profilin-2. In SKBR3 cells, upregulated proteins were RhoGDP dissociation inhibitor-α (RhoGDI-α), voltage-dependent anion channel-2, aldehyde dehydrogeanase-2 (ALDH2), LDH-A, LDH-B, pyrophosphates-1, GAPDH, cathepsin-D preprotein, F–actin capping protein β-subunit, and apolipoprotein A-I binding protein. Differential expression of RhoGDI-α, a molecule with a versatile range of biological activities in different types of breast cancer, was validated using western blotting. In conclusion, these observations using proteomics strategies serve to characterize SKBR3 and MCF7 breast cancer cell lines and offer new insights for personalized medicine on differential expression of putative drug targets between these cancer models. Further studies are warranted to examine the usefulness of SKBR3 cell line as an appropriate model for studying RhoGDI-α activities in HER2+ ER- breast cancer. Finally, we underscore that the findings presented herein also attest to an emerging strand of collaborative proteomics/OMICS studies in developing countries and resource-limited settings towards global personalized medicine, an area of postgenomics data-intensive health research that is in need of greater attention in biomedical literature.

Keywords: Breast cancer, developing world OMICS, ER, HER2, personalized medicine and developing countries, pharmacoproteomics, proteomics, RhoGDP dissociation inhibitor-α