The Role of the PI3K/AKT2 Pathway in Anti-Estrogen Resistant Breast Cancer
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Authors
Busch, Stephanie M.
Issue Date
2004
Type
Presentation
Language
en_US
Keywords
Alternative Title
Abstract
Breast cancer is one of the most common forms of cancer in women in the
western world. Estrogen has been shown to play a key role in the development
and progression of breast cancer with 2/3 of tumors expressing estrogen
receptor-α (ERα). Under prolonged exposure to endogenous estrogens, breast
tumors develop. Over the past two decades, Tamoxifen has been the most
effective anti-estrogen therapy in the treatment of ERα-positive breast cancer
(Osbourne et al., 1998). Unfortunately, patients eventually acquire resistance to
Tamoxifen within four to eight years. Previous research has shown activation
of PI3K/AKT2 and Ras/MAPK signaling pathways lead to tamoxifen resistance
(Atanaskova, N et al., 2002). The purpose of this project is to establish the role
of the PI3K/AKT2 pathway and its downstream signaling molecules,
specifically mTOR, in anti-estrogen treatment. Inhibition of mTOR signaling
by rapamycin was done to determine if p70 S6 Kinase and 4E-BP1 activation
could be inhibited. In turn, cell cycle progression and tumor growth would, in
theory, stop; therefore, tamoxifen resistance could be reversed in tumor cells
that overexpress activated AKT2. Western blot analyses were conducted to
visualize phosphorylated levels of 4E-BP1 and p70 S6 Kinase in EGFR/MCF-7
and MCF-7 cells. Overall, this research has implications for improving
estrogen-mediated breast cancer treatment with Tamoxifen.
Description
1 broadside : ill.
Diebold Scholar
Diebold Scholar
Citation
Publisher
Kalamazoo College