TY - JOUR
T1 - Genetic variation and immunohistochemical localization of the glucocorticoid receptor in breast cancer cases from the breast cancer care in Chicago cohort
AU - Al-Alem, Umaima
AU - Mahmoud, Abeer M.
AU - Batai, Ken
AU - Shah-Williams, Ebony
AU - Gann, Peter H.
AU - Kittles, Rick
AU - Rauscher, Garth H.
N1 - Funding Information:
Funding: The parent study was funded by a grant from the National Institutes of Health (2P50CA106743-Illinois at Chicago from the National Cancer Institute (Grant # 2P50CA106743-06); the National Center on Minority Health and Health Disparities (Grant # 1 P60MD003424-01); and the National Institute of Health-NHLBI (Grant # 4 R00HL140049—03).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/5/2
Y1 - 2021/5/2
N2 - 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.
AB - 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.
KW - Basal-like breast cancer
KW - Breast cancer
KW - Cytokeratin 5/6
KW - Estrogen receptor
KW - Genetic ancestry
KW - Glucocorticoid receptor
KW - Hormonal receptor
KW - Immunohistochemical localization
KW - Molecular subtypes
KW - Multispectral digital imaging
KW - Progesterone receptor
KW - Psychological stress
KW - Single nucleotide polymorphism
KW - Tissue microarrays
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U2 - 10.3390/cancers13102261
DO - 10.3390/cancers13102261
M3 - Article
AN - SCOPUS:85105755340
VL - 13
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 10
M1 - 2261
ER -