Transcriptome and proteome analyses of MCF7 cells with different expression profile of SPARC (secreted protein acidic in rich in cysteine) in the presence and absence of docetaxel.

The SPARC (secreted protein, acidic, cysteine-rich) gene encodes a 32kDa protein that belongs to a family of matricellular proteins, which interact with cell-surface receptors, growth factors, and the ECM (extracellular matrix) components. SPARC plays a role in tissue remodeling, cell migration, angiogenesis, embryonic development, tumorigenesis, and chemosensitivity. Docetaxel is an effective chemotherapeutic drug for the treatment of advanced breast cancer. However, a considerable proportion of breast cancer patients do not respond positively to docetaxel. In a previous study, we identified SPARC as differentially expressed in mammary epithelial cells expressing different levels of HER-2. In the present study, we evaluate the effects of SPARC overexpression on the sensitivity of breast cancer cells to docetaxel. MCF7 cells were transfected with the expression vector pCMV6-SPARC or pCMV6-Neo. Real-time PCR, Western blot, and immunofluorescence were used to characterize the clones overexpressing SPARC. Using cDNA microarray and label-free approach for quantitative proteomic analysis, we evaluated the transcriptome and proteome changes in the comparison of the MCF7 cell control and overexpressing SPARC before and after docetaxel treatment. Several differentially expressed genes were identified as potentially involved in SPARC-mediated chemosensitivity to docetaxel. Among the molecular interaction networks from the differentially expressed proteins, extracellular matrix and cytoskeleton remodeling were the top pathway map observed in the comparison between MCF7 cells overexpressing SPARC and the control cells before docetaxel treatment. GTP metabolism pathway was the top pathway map observed in the comparison between MCF7 cells overexpressing SPARC and the control cells after docetaxel treatment. Transcriptome and proteome integrated data resulted in forty commonly up- and downregulated genes, with the WNT pathway represented among them. Our findings suggest that SPARC expression can influence docetaxel sensitivity in MCF7 cells by modulating genes involved in diverse biologic process that might be related to drug sensitivity. (Supported by Fapesp and CNPq.) Citation Format: Ana Carolina Pavanelli, Luciana Pizzatti Barboza, Eliana Saul Furquim Werneck Abdelhay, Maria Aparecida Nagai. Transcriptome and proteome analyses of MCF7 cells with different expression profile of SPARC (secreted protein acidic in rich in cysteine) in the presence and absence of docetaxel [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; Sao Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B41.