Different Expression of Extracellular Signal-Regulated Kinases (ERK) ۱/۲ and Phospho-Erk Proteins in MBA-MB-۲۳۱ and MCF-۷ Cells after Chemotherapy with Doxorubicin or Docetaxel

Objective(s) Curative treatment of breast cancer patients using chemotherapy often fails as a result of intrinsic or acquired resistance of the tumor to the drug. ERK is one of the main components of the Ras/Raf/MEK/ERK cascade, which mediates signal from cell surface receptors to transcription factors to regulate different gene expression. In this study, cytotoxicity and the expression of Erk۱/۲ and phospho-ERK was compared in MDA-MB-۲۳۱ (ER-) and MCF-۷ (ER+) cell lines after treatment with doxorubicin (DOX) or docetaxel (DOCT). Materials and Methods Cell cytotoxicity of DOX or DOCT was calculated using MTT assay. Immonofluorescent technique was used to show MDR-۱ protein in MDA-MB-۲۳۱ and MCF-۷ cells after treatment with DOX or DOCT. The expression of ERK۱/۲ and phpspho-ERK was assayed with immunoblotting. Results Comparing IC۵۰ values showed that MDA-MB-۲۳۱ cells are more sensitive than MCF-۷ cells to DOX or DOCT. Immonofluorescent results confirmed the expression of MDR-۱ in these two cell lines after DOX or DOCT treatment. In MDA-MB-۲۳۱ cells the expression of ERK۱/۲ and phospho-ERK was decreased after DOX treatment in a dose-dependent manner. In contrast in MCF-۷ cells the expression of ERK۱/۲ and phospho-ERK was increased after DOX treatment. DOCT treatment demonstrated the same result with less significant differences than DOX. Conclusion The heterogeneity seen in cell lines actually reflects the heterogeneity of breast cancers. That is why, patients categorized in one group respond differently to a single treatment. These results emphasize the importance of a more accurate classification and a more specific treatment of breast cancer subtypes.

کلیدواژه ها:

Breast Cancer ، Docetaxel ، Doxorubicin ، MCF-۷ ، MDA-MB-۲۳۱ ، Phospho-ERK