Event Title
The Effect of Ack1 on the Chemotherapeutic Drug Susceptibility of EGFR-Dependent Lung Adenocarcinoma Cells
Faculty Mentor
Azad Gucwa
Major/Area of Research
Clinical Laboratory Science
Description
Cancer cells have the ability to overcome regulatory mechanisms that allow
for the progression of disease. One of these mechanisms involves intricate
tyrosine kinase signaling networks that transduce signals for growth, proliferation
and differentiation. Ack1 is an oncogenic kinase activated by the
epidermal growth factor receptor (EGFR), a transmembrane protein associated
with many cancer types and unregulated proliferation. Interestingly,
Ack1 has also been found to play a role in the downregulation of EGFR. The
tyrosine kinase inhibitors (TKIs) Afatinib (GilotrifÆ), Erlotinib (TarcevaÆ),
and Gefitinib (IressaÆ), are FDA-approved for the treatment of individuals
with metastatic non-small cell lung cancer (NSCLC) who test positive for
mutations in EGFR. We performed a study to determine the effect of these
inhibitors along with a relatively novel EGFR-TKI, Pelitinib, to determine
the effect of Ack1 overexpression on the drug sensitivity of HCC-827 cells,
an EGFR-dependent lung adenocarcinoma cell line. To test this, MTT cell
proliferation assays were performed on HCC-827 cells transfected with
either GFP (control) or GFP-Ack1 in the presence of multiple concentrations
of the aforementioned TKIs. Preliminary data suggests the overexpression of
Ack1 may have had an anti-proliferative effect by increasing the sensitivity
of HCC-827 to the TKIs tested; however, there was no significant difference
seen when compared to cells expressing the GFP control. Further work is
being done to finalize these results in order to gain a better understanding
of the mechanisms driving Ack1’s signaling and the role it plays in EGFR
dependent cancer progression.
The Effect of Ack1 on the Chemotherapeutic Drug Susceptibility of EGFR-Dependent Lung Adenocarcinoma Cells
Cancer cells have the ability to overcome regulatory mechanisms that allow
for the progression of disease. One of these mechanisms involves intricate
tyrosine kinase signaling networks that transduce signals for growth, proliferation
and differentiation. Ack1 is an oncogenic kinase activated by the
epidermal growth factor receptor (EGFR), a transmembrane protein associated
with many cancer types and unregulated proliferation. Interestingly,
Ack1 has also been found to play a role in the downregulation of EGFR. The
tyrosine kinase inhibitors (TKIs) Afatinib (GilotrifÆ), Erlotinib (TarcevaÆ),
and Gefitinib (IressaÆ), are FDA-approved for the treatment of individuals
with metastatic non-small cell lung cancer (NSCLC) who test positive for
mutations in EGFR. We performed a study to determine the effect of these
inhibitors along with a relatively novel EGFR-TKI, Pelitinib, to determine
the effect of Ack1 overexpression on the drug sensitivity of HCC-827 cells,
an EGFR-dependent lung adenocarcinoma cell line. To test this, MTT cell
proliferation assays were performed on HCC-827 cells transfected with
either GFP (control) or GFP-Ack1 in the presence of multiple concentrations
of the aforementioned TKIs. Preliminary data suggests the overexpression of
Ack1 may have had an anti-proliferative effect by increasing the sensitivity
of HCC-827 to the TKIs tested; however, there was no significant difference
seen when compared to cells expressing the GFP control. Further work is
being done to finalize these results in order to gain a better understanding
of the mechanisms driving Ack1’s signaling and the role it plays in EGFR
dependent cancer progression.