The DOI matches its Crossref record; 64 of the 65 references it cites were found in a registry or an index.
Overexpression of the glucose-regulated stress gene GRP78 in malignant but not benign human breast lesions
Abstract
The 78 kDa glucose-regulated stress protein GRP78 is induced by physiological stress conditions such as hypoxia, low pH, and glucose deprivation which often exist in the microenvironments of solid tumors. Activation of this stress pathway occurs in response to several pro-apoptotic stimuli. In vitro studies have demonstrated a correlation between induced expression of GRP78 and resistance to apoptotic death induced by topoisomerase II-directed drugs. We were interested in characterizing this protein in human breast lesions for potential implications in chemotherapeutic intervention. Surgical specimens of human breast lesions and paired normal tissues from the same patients were flash frozen for these studies. Total RNA and/or protein were extracted from these tissues and used in northern and/or western blot analyses, respectively, to quantify the relative expression of GRP78. Northern blot analysis indicated that 0/5 benign breast lesions, 3/5 estrogen receptor positive (ER+) breast tumors, and 6/9 estrogen receptor negative (ER-) breast tumors exhibited overexpression of GRP78 mRNA compared to paired normal tissues, with fold overexpressions ranging from 1.8 to 20. Western blot analyses correlated with these findings since 0/5 benign breast lesions, 4/6 ER+ breast tumors, and 3/3 ER- breast tumors overexpressed GRP78 protein with fold overexpressions ranging from 1.8 to 19. Immunohistochemical analysis of these tissues demonstrated that the expression of GRP78 was heterogeneous among the cells comprising different normal and malignant glands, but confirmed the overexpression of GRP78 in most of the more aggressive ER- tumors. These results suggest that some breast tumors exhibit adverse microenvironment conditions that induce the overexpression of specific stress genes that may play a role in resistance to apoptosis and decreased chemotherapeutic efficacy.
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“Many studies have found evidence of sustained and high-level activation of all three branches of the UPR (PERK, ATF6, IRE1α) in different tumors, including glioblastoma, MM, carcinomas of the breasts, stomach, esophagus, and liver [304,406,407,408,409].”
From GANAB and N-Glycans Substrates Are Relevant in Human Physiology, Polycystic Pathology and Multiple Sclerosis: A Review (2022) · cites this paper as [407]
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Cited by
The Role of Endoplasmic Reticulum Stress in Human Pathology
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The glucose-regulated proteins: stress induction and clinical applications
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The ER chaperone and signaling regulator GRP78/BiP as a monitor of endoplasmic reticulum stress
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Metadata
- Authors
- Fernandez, P. M., Tabbara, S. O., Jacobs, L. K., Manning, F. C. R., Tsangaris, T. N., Schwartz, A. M., Kennedy, K. A., & Patierno, S. R.
- Affiliations
- George Washington University (US)
- George Washington University Hospital (US)
- Venue
- Breast Cancer Research and Treatment
- Published
- 2000-01
- Volume
- 59
- Issue
- 1
- Pages
- 15-26
- ISSN
- 0167-6806 (ISSN-L)
- 1573-7217
- OpenAlex
- W1997500225
- Cited by
- 338
- References
- 65
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 8 · 2023: 8 · 2022: 9 · 2021: 10 · 2020: 20 · 2019: 15 · 2018: 13 · 2017: 14 · 2016: 13 · 2015: 21 · 2014: 26 · 2013: 19 · 2012: 26
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Breast Cancer Research and Treatment (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- GRP78, breast cancer, benign breast disease, estrogen receptor status, tumor microenvironment, apoptosis resistance, chemoresistance, topoisomerase II inhibitors, tumor aggressiveness
- MeSH terms
- Endoplasmic Reticulum Chaperone BiP, Adult, Aged, Breast Diseases, Breast Neoplasms, Carrier Proteins, Female, Heat-Shock Proteins, Humans, Immunohistochemistry, Middle Aged, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, Apoptosis, Molecular Chaperones, HSP70 Heat-Shock Proteins
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
