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• Role of the cell purinome and the transportome on liver and gastrointestinal patho-

logies.
- Study of the biliary purinome.

We will study the purinergic regulation of cholangiocytes implicating P1 receptors.

Knowledge on the cholangiocyte purinome is scarce but might be relevant to bile duct
physiology and pathophysiology. This is a CIBER EHD intramural collaboration.

• Study of the purinome and the transportome in inflammatory bowel disease.

We will functionally characterize changes in the purinome and the transportome con-

tributing to inflammatory bowel disease, by combining the use of animal models and
samples from Crohn patients. This is also an intramural CIBER EHD collaboration.

• p-t s, v-p a, C-s p, h-r i, M a, p-a M.
Most relevant érezorrasiDaLLaaNooLDaDouBeruaNoazoastorNgLaDaá
Concentrative nucleoside transporter 1 (hCNT1) promotes phenotypic changes rele-
scientific vant to tumor biology in a translocation-independent manner. Cell Death Dis. 2013

articles
May 30;4:e648.

• CrDeNas a, toLeDo C, oyarzÚN C, sepÚLveDa a, QuezaDa C, guiLLéN-góMez e. Adenosine
A(2B) receptor-mediated VEGF induction promotes diabetic glomerulopathy. Lab In-

vest. 2013 Jan;93(1):135-44.

• MeDiNa-puLiDo L, MoLiNa-arCas M, JustiCia C, soriaNo e, Burgaya F, pLaNas aM. Hypoxia and

P1 receptor activation regulate the high-affinity concentrative adenosine transporter
CNT2 in differentiated neuronal PC12 cells. Biochem J. 2013 Sep 15;454(3):437-45.

• pastor-aNgLaDa M. Transporter pharmacogenetics: do we need function? Do we need

motion? Pharmacogenomics. 2013 Oct;14(13):1537-40.

During 2013, we published the first evidence of hCNT1 being a transceptor protein
Highlights
whose loss in normal cells could contribute to oncogenesis. This study involved
both cell models as in vivo models of pancreatic adenocarcinoma. Using both it

was shown that hCNT1 restoration resulted in cell cycle arrest, cell death and

significant inhibition of tumor growth. We are now undertaking a high throughput
analysis of hCNT1 in correctal carcinoma, pancreatic cancer and hepatocarcino-

ma, in an attempt to clinically correlate hCNT1 loss with tumor stage and pro-
gression. This publication had impact in the media. On the other hand the role

CNT2 and CNT3 might play as modulators of extracellular adenosine levels and,

hence, on purinergic regulation via P1 receptors (previously shown by us to occur
in hepatocytes), was further addressed in other cell types under the framework of

inter-CIBER/REDES collaborations. Basically, it seems that CNT2 is an ubiquitous

modulator of purinergic responses. Also in 2013 an innovative and comprehensive
monography on “Pharmacogenomics of Human Drug Transporters: Clinical Im-
13
pacts”,waspublishedbyJohnWiley&Sons. Chapter11,devotedto“Nucleoside 20
transporters (SLC28 and SLC29) families” was contributed by members of the T
OR
MPET laboratory. This monography was highlighted on the webpage of the Spanish P
RE
Society of Pharmacogenetics and Pharmacogenomics. Also in this context, the PI L
of the group was invited by the journal “Pharmacogenomics” to write a critical A
NU
editorial paper on the mid-term challenges of drug transporter pharmacogenetics. N
A
Within this same framework, researchers from different CIBER were involved in D /
the organization of the international meeting of the Purine and Pyrimidine Society, H
E
held in Madrid, June 2013.
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