PED Mediates AKT-Dependent Chemoresistance in Human Breast Cancer Cells

Federico Aragona, Giorgio Stassi, Matilde Todaro, Monica Zerilli, Michela Garofalo, Gennaro Limite, Lucia Ricci-Vitiani, Giuseppe Petrella, Gerolama Condorelli, Giro Zanca, Maria Maddalena Garofalo

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)


Killing of tumor cells by cytotoxic therapies, such as chemotherapy or gamma-irradiation, is predominantly mediated by the activation of apoptotic pathways. Refractoriness to anticancer therapy is often due to a failure in the apoptotic pathway. The mechanisms that control the balance between survival and cell death in cancer cells are still largely unknown. Tumor cells have been shown to evade death signals through an increase in the expression of antiapoptotic molecules or loss of proapoptotic factors. We aimed to study the involvement of PED, a molecule with a broad antiapoptotic action, in human breast cancer cell resistance to chemotherapeutic drugs-induced cell death. We show that human breast cancer cells express high levels of PED and that AKT activity regulates PED protein levels. Interestingly, exogenous expression of a dominant-negative AKT cDNA or of PED antisense in human breast cancer cells induced a significant down-regulation of PED and sensitized cells to chemotherapy-induced cell death. Thus, AKT-dependent increase of PED expression levels represents a key molecular mechanism for chemoresistance in breast cancer.
Original languageEnglish
Pages (from-to)6668-6675
Number of pages8
JournalCancer Research
Publication statusPublished - 2005

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'PED Mediates AKT-Dependent Chemoresistance in Human Breast Cancer Cells'. Together they form a unique fingerprint.

Cite this