Genetic variation and immunohistochemical localization of the glucocorticoid receptor in breast cancer cases from the breast cancer care in Chicago cohort

Umaima Al-Alem, Abeer M. Mahmoud, Ken Batai, Ebony Shah-Williams, Peter H. Gann, Rick Kittles, Garth H. Rauscher

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number2261
JournalCancers
Volume13
Issue number10
DOIs
StatePublished - May 2 2021
Externally publishedYes

Keywords

  • Basal-like breast cancer
  • Breast cancer
  • Cytokeratin 5/6
  • Estrogen receptor
  • Genetic ancestry
  • Glucocorticoid receptor
  • Hormonal receptor
  • Immunohistochemical localization
  • Molecular subtypes
  • Multispectral digital imaging
  • Progesterone receptor
  • Psychological stress
  • Single nucleotide polymorphism
  • Tissue microarrays

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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