Amplification of WHSC1L1 regulates expression and estrogen-independent activation of ER α in SUM-44 breast cancer cells and is associated with ERα over-expression in breast cancer

The 8p11-p12 amplicon occurs in approximately 15% of breast cancers in aggressive luminal B-type tumors. Previously, we identified WHSC1L1 as a driving oncogene from this region. Here, we demonstrate that over-expression of WHSC1L1 is linked to over-expression of ER α in SUM-44 breast cancer cells and in primary human breast cancers. Knock-down of WHSC1L1, particularly WHSC1L1-short, had a dramatic effect on ESR1 mRNA and ERα protein levels. SUM-44 cells do not require exogenous estrogen for growth in vitro; however, they are dependent on ERα expression, a s ESR1 knock-down or exposure to the selective estrogen receptor degrader fulvestrant resulted in growth inhibition.

Source: Molecular Oncology - February 25, 2016 Category: Cancer & Oncology Authors: Jonathan C. Irish, Jamie N. Mills, Brittany Turner-Ivey, Robert C. Wilson, Stephen T. Guest, Alexandria Rutkovsky, Alan Dombkowski, Christiana S. Kappler, Gary Hardiman, Stephen P. Ethier Source Type: research