PTEN impacts integrity and composition of mitotic centrosomes

Abstract

<p>Loss of the tumor suppressor PTEN is observed in many human cancers, which display increased chromosome instability and aneuploidy. The subcellular fractions of PTEN are associated with different functions that regulate cell growth, invasion and chromosome stability. In this study we show a novel role for PTEN in regulating mitotic centrosomes. Localization of PTEN to mitotic centrosomes peaks between prophase and metaphase, paralleling the staining of gamma-tubulin and coinciding with the time frame of centrosome maturation. Knockdown of PTEN reduced gamma-tubulin at mitotic centrosomes and led to reduced global levels of gamma-tubulin during nocodazole-induced mitotic arrest. The reduction of gamma- tubulinmay contribute to the defects in centrosome number and chromosome segregation observed after knockdown of PTEN. The intensity and localization of PTEN at mitotic centrosomes was also impaired in more tumorigenic cell lines as compared to primary cells, indicating that recruitment of PTEN to mitotic centrosomes plays a role in chromosome stability and possibly cancer progression.</p>