Therapeutic Discovery Targeting the Intracellular MUC1 C-terminal Domain Inhibits Proliferation and Estrogen Receptor Transcriptional Activity in Lung Adenocarcinoma Cells

Mucin 1 (MUC1) is a diagnostic factor and therapy target in lung adenocarcinoma. MUC1 C-terminal intracellular domain (CD) interacts with estrogen receptor (ER) a and increases gene transcription in breast cancer cells. Because lung adenocarcinoma cells express functional ERa and ERb, we examined MUC1 expression and MUC1–ER interaction. Because blocking MUC1 CD with an inhibitory peptide (PMIP) inhibited breast tumor growth, we testedwhether PMIPwould inhibit lung adenocarcinoma cell proliferation. We report that MUC1 interacts with ERa and ERbwithin the nucleus of H1793 lung adenocarcinoma cells in accordancewithMUC1 expression. PMIPwas taken up byH23 andH1793 cells and inhibited the proliferation of H1793, but not H23 cells, concordant with higher MUC1 protein expression in H1793 cells. Lower MUC1 protein expression in H23 does not correspond to microRNAsmiR-125b andmiR-145 that have been reported to reduce MUC1 expression. PMIP had no effect on the viability of normal human bronchial epithelial cells, which lackMUC1 expression. PMIP inhibited estradiol-activated reporter gene transcription and endogenous cyclin D1 and nuclear respiratory factor-1 gene transcription in H1793 cells. These results indicate MUC1–ER functional interaction in lung adenocarcinoma cells and that inhibiting MUC1 inhibits lung adenocarcinoma cell viability. Mol Cancer Ther; 10(11); 2062–71. 2011 AACR.