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The Proton-Coupled Folate Transporter: Impact on Pemetrexed Transport and on Antifolates Activities
 

Summary: The Proton-Coupled Folate Transporter: Impact
on Pemetrexed Transport and on Antifolates Activities
Compared with the Reduced Folate Carrier
Rongbao Zhao, Andong Qiu, Eugenia Tsai, Michaela Jansen, Myles H. Akabas, and
I. David Goldman
Departments of Medicine (R.Z., M.H.A., I.D.G.), Molecular Pharmacology (R.Z., A.Q., E.T., I.D.G.), and Physiology and
Biophysics (M.J., M.H.A.), Albert Einstein College of Medicine, Bronx, New York
Received January 16, 2008; accepted June 3, 2008
ABSTRACT
The reduced folate carrier (RFC) and the proton-coupled folate
transporter (PCFT) are ubiquitously expressed in normal and
malignant mammalian tissues and in human solid tumor cell
lines. This article addresses the extent to which PCFT contrib-
utes to transport of pemetrexed and to the activities of this and
other antifolates relative to RFC at physiological pH. Either RFC
or PCFT cDNA was stably transfected into a transporter-null
HeLa cell variant to achieve activities similar to their endoge-
nous function in wild-type HeLa cells. PCFT and RFC produced
comparable increases in pemetrexed activity in growth medium
with 5-formyltetrahydrofolate. However, PCFT had little or no

  

Source: Akabas, Myles - Department of Physiology and Biophysics, Albert Einstein College of Medicine, Yeshiva University

 

Collections: Biology and Medicine