Genetic Variation and Immunohistochemical Localization of the Glucocorticoid Receptor in Breast Cancer Cases from the Breast Cancer Care in Chicago Cohort

Abstract

Background: Glucocorticoid, one of the primary mediators of stress, acts via its receptor, the glucocorticoid receptor (GCR/NR3C1), to regulate a myriad of physiological processes. We measured the genetic variation and protein expression of GCR, and the genes that regulate GCR function or response and examined whether these alterations were associated with breast cancer clinicopathological characteristics. Method: We used samples from a multiracial cohort of breast cancer patients to assess the association between breast cancer characteristics and the genetic variants of single nucleotide polymorphisms (SNPs) in GCR/NR3C1, FKBP5, Sgk1, IL-6, ADIPOQ, LEPR, SOD2, CAT, and BCL2. Results: Several SNPs were associated with breast cancer characteristics, but statistical significance was lost after adjustment for multiple comparisons. GCR was detected in all normal breast tissues and was predominantly located in the nuclei of the myoepithelial cell layer, whereas the luminal layer was negative for GCR. GCR expression was significantly decreased in all breast cancer tissue types, compared to nontumor tissue, but was not associated with breast cancer characteristics. We found that high nuclear GCR expression was associated with basal cell marker cytokeratin 5/6 positivity. Conclusion: GCR expression is reduced in breast cancer tissue and correlates with the basal cell marker CK5/6.

Prognostic Value of SGK1 and Bcl-2 in Invasive Breast Cancer

“…Pathologists at the University of Illinois Hospital initially diagnosed cases as invasive breast cancer, fibroadenoma (benign breast tumors of both glandular and stromal tissue), or non-tumoral breast tissues during the routine analysis of surgically obtained specimens (the whole sections before TMA construction). Then, three pathologists evaluated the cores independently and confirmed the diagnosis, as described in our previous publications [ 13 , 21 ]. The methods used to design the issue microarray have been described, in detail, in our previous reports [ 13 , 21 ].…”

“…Then, three pathologists evaluated the cores independently and confirmed the diagnosis, as described in our previous publications [ 13 , 21 ]. The methods used to design the issue microarray have been described, in detail, in our previous reports [ 13 , 21 ]. Briefly, the tissue microarrays (TMA) contained tumor tissue from 280 cases, 26 normal breast tissues from unaffected women obtained by reduction mastectomy procedures, and 6 fibroadenomas from UIC Medical Center in the tissue microarray.…”

“…As previously described, histological sections were then incubated with the proper primary antibodies (listed in Table 1 ), followed by the proper secondary antibodies. Finally, sections were stained with 3,3-diaminobenzidine (DAB) and the counterstain, hematoxylin [ 13 ]. Respective TMAs were stained for each protein separately.…”

“…Our previous study showed reduced GCR protein expression in breast cancer tissue [ 13 ]. In this study, our main objective is to understand if there is a correlation between GCR reduction and its two downstream target genes, serum and glucocorticoid-regulated kinase-1 (SGK1) [ 14 ] and B-cell lymphoma 2 (Bcl-2), from the respective tissue arrays [ 15 ].…”

Effects of hypericin encapsulated on Pluronic F127 photodynamic therapy against triple negative breast cancer

“…Breast cancer (BC), one of the leading causes of death among women is a complex disease in which genetic, epigenetic and environmental factors are implicated in its initiation and progression (Al-Alem et al, 2021). BC is also a heterogeneous disease that can be subdivided depending on the enrichment status of hormone receptors and human epidermal growth factor receptor 2 (HER2), respectively.…”