Title |
Regulation of c-myc translation by hnRNP A1: role in multiple myeloma tumor respo
|
Institution |
BRENTWOOD BIOMEDICAL RESEARCH INSTITUTE, LOS ANGELES, CA
|
Principal Investigator |
GERA, JOSEPH
|
NCI Program Director |
Kevin Howcroft
|
Cancer Activity |
Immunology
|
Division |
DCB
|
Funded Amount |
$264,964
|
Project Dates |
07/01/2008 - 05/31/2014
|
Fiscal Year |
2012
|
Project Type |
Grant
|
Research Topics w/ Percent Relevance |
Cancer Types w/ Percent Relevance |
Cancer (100.0%)
|
Multiple Myeloma (100.0%)
|
Research Type |
Cancer Initiation: Oncogenes and Tumor Suppressor Genes
Cancer Progression and Metastasis
|
Abstract |
DESCRIPTION (provided by applicant): The long range goal of the proposal is to investigate the mechanism of cap-independent translation of the c-myc protein with the assumption that its cellular function is a key determinant of tumor cell responses, especially for the malignancy multiple myeloma. More specifically, the proposal will elucidate how hnRNP A1 (A1) functions as a trans-acting protein that binds to the internal ribosome entry site (IRES) in the 5' UTR of the c-myc transcript, thus facilitating IRES-dependent translation of myc. Furthermore, it will focus on the ability of Akt and MAPK cascades to regulate this A1 translation-promoting activity, testing effects on the IRES-annealing activity of A1, effects on IRES-ribosome binding and effects on A1/IRES subcellular localization. Multiple myeloma cell lines, primary tumor cells and xenograft models will be used to exploit the insight gained on A1/myc IRES regulatory controls to understand mechanisms of myeloma progression due to IL-6 stimulation and myeloma therapy-resistance when treatment with mTOR inhibitors is attempted. |