Ras-MEK Signaling Pathway Confers Growth Factor Independence in Erythroleukemia Cell Line UT-7
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Biological and Environmental Sciences
Date of Award
Summer 2023
Abstract
Acute myeloid leukemia (AML) is a heterogeneous group of blood disorders in whichover-proliferation and lack of differentiation lead to nonfunctional myeloblasts. The most common form of leukemia in the United States is AML and it has a poor prognosis in patients with a cure rate of 15%. The Ras-MAPK pathway is suggested to drive proliferation in AML and 12-27% of AML cases have a mutation in this pathway. The UT7-GF cell line, an AML cell line generated in our laboratory grows and proliferates without growth factors. Based upon these results, we hypothesized that the proliferative capabilities of the AML cell line in serum-free media are due to the deregulation of the RAS-ERK signaling pathway. The mitogen-activated protein kinase (MAPK) pathway consists of the Ras-Raf-MEK-ERK signaling cascade that is activated by a series of phosphorylations leading to the translocation in ERK1/2 into the nucleus to turn on genes that regulate growth and proliferation. In proliferation assays, unlike the growth factor-dependent parental UT7-EPO cells, the UT7-GF cells survived in the absence of serum. Immunoblot analysis using phosphospecific antibody detected hyperphosphorylation of p44/42 (ERK) and p38 (MEK1) in UT7-GF cells suggesting constitutive activation of Ras-MEK-ERK pathway. U0126, an inhibitor of MEK1, abrogated the phosphorylation of p44/42 and p38 in UT7-GF cells. Consequently, U0126 treatment reduced the viability of UT7-GF with an IC50 of 0.96μM. In summary, we identified a direct role for constitutively active MEK-ERK pathway in the growth and proliferation of an AML cell line without serum growth factors. Therefore, interrupting the ERK-MEK pathway could potentially improve clinical outcomes in AML.
Advisor
Venugopalan Cheriyath
Subject Categories
Biology | Life Sciences
Recommended Citation
Ver Steeg, Mickilee, "Ras-MEK Signaling Pathway Confers Growth Factor Independence in Erythroleukemia Cell Line UT-7" (2023). Electronic Theses & Dissertations. 1119.
https://digitalcommons.tamuc.edu/etd/1119
