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KMID : 1140120100150010045
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Cancer Prevention Research
2010 Volume.15 No. 1 p.45 ~ p.51
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Effect of GRP78 Overexpression on Antiproliferative Activity of Anticancer Agents against Breast Cancer Cells
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Ha Young-Ran
Lee In-Ae
Kim Hyo-Jung
Kang Hee-Jung
Nam Dae-Hwan
Park Ji-A
Kim Jong-Sang
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Abstract
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Our previous study showed that genistein, a tyrosine kinase inhibitor and one of the major isoflavones in soybean, induced the expression of glucose regulated protein 78 (GRP78) which is one of the heat shock proteins in both MCF-7 and MDA-MB-231 cells. Pretreatment with genistein caused the increased resistance to doxorubicin in mammary tumor MCF-7 cells while it sensitized estrogen receptor (ER)-negative mammary tumor MDA-MB-231 cells to the drug. To address the discrepancy in response to the drug between two different cell lines pretreated with genistein, the transfectants expressing high level of GRP78 were generated by transfecting with pcDNA3.1 vector carrying GRP78 gene. Overexpression of GRP78 did not affect the cell morphology but modulated the expression of a set of genes involved in cell expressing different levels of GRP78 survival in cell type-specific manner. The transfectants were used to evaluate whether the level of GRP78 regulates the resistance or sensitivity against anti-cancer drugs including doxorubicin, tamoxifen, paclitaxel, mitomycin C. Overexpression of GRP78 made MCF-7 cells more resistant to doxorubicin and mitomycin C, and it slightly sensitized MDA-MB-231 cells to tamoxifen and paclitaxel. In conclusion, the cellular level of GRP78 or any exogenous factor affecting GRP78 expression may alter the efficacy of anticancer drugs on mammary tumor cells.
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KEYWORD
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Doxorubicin, Glucose-regulated protein78 (GRP78), Anticancer drugs, Mammary tumor, Drug resistance
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