Publication Type |
honors thesis |
School or College |
College of Science |
Department |
Chemistry |
Faculty Mentor |
Sheri L. Holmen |
Creator |
Arave, Rowan A. |
Title |
AKT1 activation promotes the development of melanoma metastasis |
Year graduated |
2015 |
Date |
2015-12 |
Description |
Metastases are the major cause of melanoma-related mortality. Previous studies implicating aberrant AKT (or protein kinase B) signaling in human melanoma metastases led to the evaluation of the effect of activated AKT1 expression in non-metastatic BRAFV600E/cyclin dependent kinase inhibitor 2a null (Cdkn2aNuU) mouse melanomas invivo. Expression of activated AKT1 resulted in highly metastatic melanomas with lung and brain metastases in 67% and 17% of the mice, respectively. Interestingly, silencing of the phosphatase and tensin homolog (PTEN) in BRAFV600E/Cdkn2aNuU melanomas with lung and brain metastases in 67% and 17% of the mice, respectively. Interestingly, silencing of the Phosphatase and tensin homolog (PTEN) in BRAFV600E/Cdkn2aNuU melanomas cooperated with activated AKT1 resulting in decreased tumor latency and the development of lung and brain metastases in nearly 80% of tumor-bearing mice. These data demonstrate that AKT1 activation is sufficient to elicit lung and brain metastases in this context and Eveal that activation of AKT1 is distinct from PTEN silencing in metastatic melanoma progression. These findings advance knowledge of the mechanisms cooperated with activated AKT1 resulting in decreased tumor latency and the development of lung and brain metastases in nearly 80% of tumor-bearing mice. These data demonstrate that AKT1 activation is sufficient to elicit lung and brain metastases in this context and reveal that activation of AKT1 is distinct from PTEN silencing in metastatic melanoma progression. These findings advance knowledge of the mechanisms driving melanoma metastasis and may provide valuable insights for clinical management of this disease development of lung and brain metastases in nearly 80% of tumor-bearing mice. These data demonstrate that AKT1 activation is sufficient to elicit lung and brain metastases of this disease. |
Type |
Text |
Publisher |
University of Utah |
Subject |
Melanoma; genetics; research; metastasis; genetics; research; biochemistry; genetics |
Language |
eng |
Rights Management |
© Rowan A. Arave |
Format Medium |
application/pdf |
Format Extent |
25,399 bytes |
Identifier |
etd3/id/3688 |
Permissions Reference URL |
https://collections.lib.utah.edu/ark:/87278/s6v15tw3 |
ARK |
ark:/87278/s6fj5r4v |
Setname |
ir_htoa |
ID |
197239 |
Reference URL |
https://collections.lib.utah.edu/ark:/87278/s6fj5r4v |