Item Details

abstract

The serine/threonine kinase, Akt, is a central signaling hub linked to multiple cellular processes. The three mammalian isoforms of Akt (Akt1, Akt2, and Akt3) share common structural and functional characteristics. Despite their common features and shared activation pathway, the Akt isoforms exhibit divergent regulation of downstream processes. The molecular basis for these differences is unknown. Of the three isoforms, Akt2 was found to be uniquely regulated by hydrogen peroxide (H2O2), an established secondary messenger molecule. Akt2 kinase activity is reversibly inhibited by H2O2. This isoform has been implicated in the regulation of glucose homeostasis with Akt2 knockout mice displaying a type 2 diabetes mellitus (T2DM) like phenotype. Humans with mutation in the kinase domain of Akt2 exhibit severe insulin resistance. Additionally, increases in overall Akt expression have been linked to increased risk of breast cancer metastasis and poorer breast cancer prognosis. Hypotheses proposed to explain the increased cancer risk vary widely but none thus far have explored redox regulation of Akt2. Here, it was hypothesized that the relative balance of activating phosphorylation and inhibitory oxidative modification of Akt2 play critical functions in breast cancer progression through differential regulation of glucose uptake, cell cycle, migration, and invasion properties. The work presented here lays the foundations for further investigations into the role of Akt2 in breast cancer progression in relation to T2DM.

subject

Akt2

Breast Cancer

Diabetes

Reactive Oxygen Species

Redox-biology

contributor

Wieland, Robert (author)

Furdui, Cristina M (committee chair)

Watabe, Konosuke (committee member)

date

2018-05-24T08:36:16Z (accessioned)

2018 (issued)

degree

Molecular Medicine and Translational Science (discipline)

2023-05-22 (liftdate)

embargo

2023-05-22 (terms)

identifier

http://hdl.handle.net/10339/90749 (uri)

language

en (iso)

publisher

Wake Forest University

title

Akt2 Redox-regulation in Breast Cancer and Diabetes

type

Thesis