Cell and Tissue Signaling

Tuesday, October 18, 2005 3:00 PM-5:00 PM Exhibit Hall

(PP257) The Akt/PKB survival pathway: a role for isoform specificity in breast cancer.

Santi, Stacey*,1, 2, Lee, Hoyun 1, 2, 1 University of Ottawa, Ottawa, Ontario, Canada2 Northeastern Ontario Regional Cancer Centre (NEORCC), Sudbury, Ontario, Canada

ABSTRACT- Accumulating lines of evidence suggest that activation of the serine/threonine kinase Akt (protein kinase B/PKB) is involved in promoting cancer cell survival by mediating resistance to cancer therapies. Akt kinase regulates cell survival and apoptotic cell death through interactions with downstream signaling intermediates such as caspase-9, Bad, and GSK-3, among others. The Akt/PKB family comprises three members, Akt1, Akt2 and Akt3, all of which show high sequence similarity. It is not currently known if the Akt isoforms are functionally redundant for cellular survival during radiation treatment. In the present study, MDA-MB 231 and MDA-MB 468 breast cancer cells were treated with X-ray radiation at two different doses (5 Gy and 9 Gy). Isoform-specific protein expression levels and subcellular localization of the isoforms were examined at various timepoints post-irradiation. Differential levels of endogenous protein expression and subcellular localization were found for each of the isoforms. We are currently in the process of examining the role of each Akt isoform in the regulation of cell survival in response to ionizing radiation.

Key words: Akt, Akt isoforms, X-ray radiation, breast cancer

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2005 RRS