IL‐1 induces p62/SQSTM1 and autophagy in ERα+/PR+ BCa cell lines concomitant with ERα and PR repression, conferring an ERα−/PR− BCa‐like phenotype. Issue 2 (15th October 2018)

• Record Type: Journal Article
• Authors: Nawas, Afshan Fathima; Mistry, Ragini; Narayanan, Shrinath; Thomas‐Jardin, Shayna Elizabeth; Ramachandran, Janani; Ravichandran, Jananisree; Neduvelil, Ebin; Luangpanh, Krisha; Delk, Nikki Ayanna
• Is Part Of: Journal of cellular biochemistry. Volume 120:Issue 2(2019)
• Page Start: 1477
• Page End: 1491
• Publication Date: 2018-10-15
• Subjects: autophagy -- endocrine resistance -- estrogen receptor α -- interleukin‐1 -- p62/SQSTM1; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.27340
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Estrogen receptor α (ERα) low/− tumors are associated with breast cancer (BCa) endocrine resistance, where ERα low tumors show a poor prognosis and a molecular profile similar to triple negative BCa tumors. Interleukin‐1 (IL‐1) downregulates ERα accumulation in BCa cell lines, yet the cells can remain viable. In kind, IL‐1 and ERα show inverse accumulation in BCa patient tumors and IL‐1 is implicated in BCa progression. IL‐1 represses the androgen receptor hormone receptor in prostate cancer cells concomitant with the upregulation of the prosurvival, autophagy‐related protein, Sequestome‐1 (p62/SQSTM1; hereinafter, p62); and given their similar etiology, we hypothesized that IL‐1 also upregulates p62 in BCa cells concomitant with hormone receptor repression. To test our hypothesis, BCa cell lines were exposed to conditioned medium from IL‐1‐secreting bone marrow stromal cells (BMSCs), IL‐1, or IL‐1 receptor antagonist. Cells were analyzed for the accumulation of ERα, progesterone receptor (PR), p62, or the autophagosome membrane protein, microtubule‐associated protein 1 light chain 3 (LC3), and for p62‐LC3 interaction. We found that IL‐1 is sufficient to mediate BMSC‐induced ERα and PR repression, p62 and autophagy upregulation, and p62‐LC3 interaction in ERα + /PR + BCa cell lines. However, IL‐1 does not significantly elevate the high basal p62 accumulation or high basal autophagy in the ERα − /PR − BCa cell lines. Thus, our observations imply that IL‐1 confers a prosurvival ERα − /PR − molecular phenotype in ERα + /PR + BCa cells that may be dependent on p62 function and autophagy and may underlie endocrine resistance. Abstract : IL‐1 represses hormone receptors and induces p62 and autophagy upregulation and interaction in ER + /PR + BCa cell lines. p62 and autophagy are prosurvival and basally high in ER − /PR − BCa cell lines. Thus, IL‐1 confers an ER − /PR − molecular phenotype on ER + /PR + BCa cells that may promote cell survival when hormone receptors are reduced or lost.