Hypoxia-inducible factor 1A inhibition overcomes castration resistance of prostate tumors

ABSTRACT: Androgen deprivation therapy (ADT) is a cornerstone of prostate cancer (PCa) management. Although tumors initially regress, many progress to a hormone-independent state termed castration-resistant PCa (CRPC), for which treatment options are limited. We here report that the major luminal cell population in tumors of Pten(i)pe-/- mice, generated by luminal epithelial cell-specific deletion of the tumor suppressor PTEN after puberty, is castration-resistant, and that the expression of inflammation and stemness markers is enhanced in persistent luminal cells. In addition, hypoxia-inducible factor 1 (HIF1) signaling, which we have previously demonstrated to be induced in luminal cells of Pten(i)pe-/- mice and to promote malignant progression, is further activated. Importantly, we show that gene

SUBMITTER: Ms. Julie Terzic 

PROVIDER: S-SCDT-10_15252-EMMM_202217209 | biostudies-other |

REPOSITORIES: biostudies-other