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De‐regulation of GRP stress protein expression in human breast cancer cell lines

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Abstract

The stress‐inducible glucose regulated proteins (GRPs), a class of calcium‐binding molecular chaperones localized in the endoplasmic reticulum, have been implicated in the development of tumorigenicity, drug resistance, and cytotoxic immunology. This study investigates the expression pattern of GRP94 and GRP78 in a panel of breast carcinoma cell lines, as compared to two independently derived normal human breast epithelial cell lines. Here we report that a 3‐ to 5‐fold increase in the basal level of the GRP94 protein was observed in all five breast carcinoma cell lines examined. The increase was independent of either the p53 or estrogen receptor status of the breast carcinomas. In carcinoma cells deprived of glucose, mimicking the conditions in poorly vascularized solid tumors, up to 9‐fold induction of GRP94 was observed relative to the basal level expressed in a normal breast epithelial cell line. Interestingly, while the majority of the breast cancer cell lines can respond to tunicamycin‐ and thapsigargin‐induced stress by increasing the steady state levels of grp94 and grp78 transcripts, the induction at the GRP protein level is variable and does not always correspond with the transcript level. Further, we discovered that one of the human breast carcinoma cell lines, MCF‐7, has specifically lost its ability to respond to tunicamycin stress.

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  1. Department of Biochemistry and Molecular Biology, USC/Norris Comprehensive Cancer Center, University of Southern California School of Medicine, Los Angeles, CA, USA

    Gadi Gazit, Jun Lu & Amy S. Lee

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Gazit, G., Lu, J. & Lee, A.S. De‐regulation of GRP stress protein expression in human breast cancer cell lines. Breast Cancer Res Treat 54, 135–146 (1999). https://doi.org/10.1023/A:1006102411439

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