Glucocorticoids, 3-Ketosteroids Adversely Affect Breast Cancer
(HealthDay News) — Glucocorticoids and other 3-ketosteroids may adversely affect patients with mixed estrogen receptor (ER) α-positive/cytokeratin-5 (CK5) breast cancer, according to a study published online June 22 in Oncogene.
The authors note that a subgroup of ERα-positive breast cancer is characterized by a minor population of ERα-negative cancer cells expressing the basal CK5, which are therapy resistant. With this in mind, Chelain R. Goodman, from Thomas Jefferson University in Philadelphia, and colleagues examined whether 3-ketosteroids other than progestins can induce CK5-positive cells.
The researchers found that glucocorticoids and mineralocorticoids expand the CK5-positive cell population. In vitro and in vivo, 3-ketosteroid-induced CK5-positive cells lacked ERα and progesterone receptors, expressed stem cell marker CD44, and exhibited elevated clonogenicity in soft agar and broad drug resistance. CK5-positive cell upregulation by 3-ketosteroids required induction of the transcription repressor BCL6, based on BCL6 suppression by two independent BCL6 shRNAs or prolactin. In vivo, prolactin also suppressed 3-ketosteroid-induction of CK5-positive cells in T47D xenografts. In two independent patient cohorts, survival analysis with recursive partitioning in node-negative ERα-positive breast cancer using quantitative CK5 and BCL6 or protein expression data identified the risk of recurrence.
"The observations further suggest a cooperative diagnostic utility of CK5 and BCL6 expression levels and justify exploring efficacy of inhibitors of BCL6 and 3-ketosteroid receptors for a subset of ERα-positive breast cancers," the authors write.