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Regulation Of Igfbp-1 Phosphorylation In Hypoxia Via Mtor Signaling, Ian Damerill
Regulation Of Igfbp-1 Phosphorylation In Hypoxia Via Mtor Signaling, Ian Damerill
Electronic Thesis and Dissertation Repository
In this study, we provide novel evidence for a role of fetal liver mTOR signaling in regulating IGF-I bioavailability by modulating IGFBP-1 phosphorylation due to hypoxia – a key factor in the development of reduced fetal growth in utero. We utilized HepG2 cells in vitro and demonstrated a link between mTOR inhibition and hypoxia-induced IGFBP-1 phosphorylation. Using a biological assay for IGF-I receptor autophosphorylation, we demonstrated a functional significance for hypoxia-induced IGFBP-1 phosphorylation in reducing IGF-I bioactivity in vitro. Further, we have implicated a mechanistic link to increased CK2 activity within this regulation. We demonstrate that mTOR inhibition …
Pi3k- And Mtor-Dependent Mechanisms Of Lapatinib Resistance And Resulting Therapeutic Opportunities, Samuel Brady
Pi3k- And Mtor-Dependent Mechanisms Of Lapatinib Resistance And Resulting Therapeutic Opportunities, Samuel Brady
Dissertations & Theses (Open Access)
Breast cancers with HER2 amplification represent 20-25% of breast cancer cases and are frequently responsive to the HER2 kinase inhibitor lapatinib, but generally for only short duration. We aimed to understand how breast cancers with HER2 amplification become resistant to lapatinib, in order to identify potential therapies that can overcome lapatinib resistance. To establish lapatinib resistance models we treated three HER2+ breast cancer cell lines with lapatinib for several months until they became lapatinib-resistant. We then compared lapatinib-sensitive (parental) cells with their lapatinib-resistant (LapR) counterparts to identify changes conferring lapatinib resistance. We found that activation of PI3K, specifically the p110α …
Lipid Dependence In Ras-Driven Tumors, Darin Salloum
Lipid Dependence In Ras-Driven Tumors, Darin Salloum
Dissertations, Theses, and Capstone Projects
Over past decade, metabolic alterations in cancer cells have received a substantial amount of interest. It had been established that cancer cells undergo a significant amount of metabolic alterations, and some of these alterations are similar to those in normal highly proliferative cells. However, it is becoming more apparent that many of the metabolic alterations are specific to particular oncogenic signaling pathways. Although altered metabolic machinery makes cancer cells more efficient at promoting growth when nutrients are supplied at the sufficient amounts, the dependency of cancer cells on particular metabolic reprogramming deems cancer cells susceptible to disruptions within metabolic network. …
Metabolic Checkpoints In Cancer Cell Cycle, Mahesh Saqcena
Metabolic Checkpoints In Cancer Cell Cycle, Mahesh Saqcena
Dissertations, Theses, and Capstone Projects
Growth factors (GFs) as well as nutrient sufficiency regulate cell division in metazoans. The vast majority of mutations that contribute to cancer are in genes that regulate progression through the G1 phase of the cell cycle. A key regulatory site in G1 is the growth factor-dependent Restriction Point (R), where cells get permissive signals to divide. In the absence of GF instructions, cells enter the quiescent G0 state. Despite fundamental differences between GF signaling and nutrient sensing, they both have been confusingly referred to as R and therefore by definition considered to be a singular event in G1. Autonomy from …