Abstract 1123: PTEN loss increases efficiency of breast tumor metastasis

Abstract

Abstract Breast cancer is the most frequent malignancy in women, and although many breast cancers are curable via surgery, approximately one quarter maintain a latent and insidious characteristic of slow growth with early metastasis. The loss of the tumor suppressor PTEN has been associated with breast cancer stage, lymph node status, and disease-related death, and the high rate of loss in primary tumors suggests a potential role in initiation and/or progression of the disease. However, specific cellular alterations in human breast epithelium controlled by PTEN inactivation, which lead to an increased metastatic phenotype, remain poorly defined. We have determined that heterozygous and homozygous loss of PTEN in non-tumorigenic mammary epithelial cells (MECs) was insufficient to promote anchorage-independent growth. However, MECs with PTEN loss maintained elevated activation of the PI3K/Akt and MAPK pathways and apoptotic resistance to cell rounding and matrix detatchment. We have also recently determined that PTEN expression loss leads to the production of long, dynamic, tubulin-based membrane protrusions upon detachment, which are increased in frequency, number and length per cell as compared to their isogenic, PTEN-expressing parental counterparts. These novel structures, termed microtentacles (McTNs), are structurally distinct from classical actin-based extensions of adherent cells, persist for days in breast tumor lines that are resistant to anoikis, and aid in the reattachment to matrix or cell monolayers. Therefore, the combination of apoptotic resistance and enhanced McTN formation due to PTEN loss may have important consequences for facilitating tumor cell extravasation and efficient adherence in metastatic sites. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1123.