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VACM-1!
By Michael Hledin and Gabe Marquez
Introduction
VACM-1 stands for Vasopressin-Activated
Calcium Mobilizing Receptor AKA Cullin5
• It encodes a protein called 93 kDa, and
inhibits (stops) cellular growth.
• VACM-1 is naturally expressed in blood
vessel cells and is associated with
complexes that destroy proteins in the cell.
Uses on cancer
• VACM-1 stops cell growth, therefore, if
used on cancer cells, it should stop the
growth of cancerous tumors on cells.
Hypothesis
• If we increase VACM1 in vascular cells it
will decrease cell growth which will help
prevent cancer cell growth.
• If we increase VACM1 in cancerous cells,
it will decrease also cell growth.
What We Do
• We mutate VACM-1 in cells and look at
changes in cell growth.
• Our method is to find a drug to induce
growth of VACM-1 in cells.
Method 1
• Our first method is for RAMEC cells, which are
found in rats. We take a plate of cells as shown
below, and scratch a cross into each well. We
then treat the cells with different doses of a drug,
called PMA which induces cell growth. After the
cells are treated, we monitor their growth for a
few days. If the scratch has increased or gotten
wider, then the drugs have stopped or slowed
cell growth, but if it has gotten smaller, the drugs
have increased cell growth.
Method 2
• Our second method is for T47D cells which are
the primary cancer cells. Since these grow
slower then RAMEC cells, it would take too long
to scratch them. Therefore, we simply count the
number of cells we have before and after we
treat them. In these cells, we use a drug called
resveratrol which is found in wine. Below we
have graphs that show the effect that different
doses of resveratrol had on T47D cells.
40 ug/ml Resveratrol
5 ug/ml Resveratrol
90.00%
Change in Growth
100.00%
80.00%
60.00%
CMV Control Cells
40.00%
VACM-1 Transfected
cells
20.00%
Change in Growth
120.00%
40.00%
-10.00%
CMV control cells
0
1
VACM-1 Transfected
cells
-60.00%
0.00%
-20.00%
0
1
3
-110.00%
Time (days)
-40.00%
Time(days)
3
Conclusions
• When cells that had VACM1 were treated
with drugs, growth was decreased much
more then in cells with no VACM1. This
makes VACM1 an important regulator of
cell growth and a target for cancer drugs.
Acknowledgements
•
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The REACH Program
Professor Hledin
The Hledin lab especially Justin Lubbers
Mrs. Harper
Biology and Chemistry departments
Hope College