Title: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?
VOLUME: 10 ISSUE: 2
Author(s):Zahra Mojtahedi, Nasrollah Erfani and Abbas Ghaderi
Affiliation:Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences, Shiraz, Iran.
Keywords:Breast cancer, developing world OMICS, ER, HER2, personalized medicine and developing countries,
pharmacoproteomics, proteomics, RhoGDP dissociation inhibitor-α
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.
