Data from Divergent Activity of the Pseudogene <i>PTENP1</i> in ER-Positive and Negative Breast Cancer

Abstract

<div>Abstract<p>Transcripts derived from the <i>PTEN pseudogene (PTENP1)</i> function as decoys to adsorb miRNAs targeting the <i>PTEN</i> tumor suppressor for degradation, and <i>PTENP1</i> upregulation is known to inhibit growth in preclinical cancer models. Here, <i>PTENP1</i> 3′UTR transduction influences PTEN, AKT/mTOR signaling, and tumor progression in estrogen receptor (ER)-positive and -negative breast cancer cells. <i>PTENP1</i> upregulation decreases <i>PTEN</i> gene expression in the ER-positive MCF7 and T47D human breast carcinoma cells and accelerates MCF7 tumor growth <i>in vivo</i>. Of note, <i>PTENP1</i> transduction significantly decreases ERα (<i>ESR1</i>) mRNA and protein levels in MCF7 xenografts with a concomitant increase in hsa-miR-26a, a miRNA known to target <i>ESR1</i>. In the ER-negative MDA-MB-231 and C3HBA breast cancer cells, upregulation of <i>PTENP1</i> increases <i>PTEN</i> gene expression with no influence on hsa-miR-26a, <i>ESR1</i>, or ERα expression. While <i>PTENP1</i> transduction did not influence the growth rate of human MDA-MB-231 xenografts, <i>PTENP1</i> upregulation profoundly reduces its metastatic propensity. Furthermore, <i>PTENP1</i> significantly inhibits the growth rate of ER-negative C3HBA murine breast cancer xenografts. <i>PTENP1</i> transduction had no influence on doxorubicin cytotoxicity in ER-positive MCF7 cells but an increase in doxorubicin sensitivity was observed in the ER-negative MDA-MB-231 cells. In summary, while <i>PTENP1</i> upregulation decreased <i>PTEN</i> transcript levels and stimulated the growth of ER-positive breast cancers, increased <i>PTEN</i> transcript levels and inhibited tumor progression was observed in the ER-negative cells.</p><p><b>Implications:</b> This report highlights the profound biological activity of <i>PTENP1</i> in breast cancer, which is dictated by the hormone receptor status. <i>Mol Cancer Res; 16(1); 78–89. ©2017 AACR</i>.</p></div>