Increased expression of prostaglandin reductase 1 in hepatocellular carcinomas from clinical cases and experimental tumors in rats.
To identify novel tumor-associated proteins, we analyzed the protein expression patterns from experimental hepatocellular carcinoma (HCC) that were induced using hepatocarcinogenesis models in rats. Rats were subjected to two previously described protocols of hepatocarcinogenesis using diethylnitrosamine as a carcinogen: the alternative Solt-Farber (aS&F) protocol, which induces HCC within 9 months, and Schiffer's model, which induces cirrhosis and multifocal HCC within 18 weeks. The patterns of protein expression from tumors and normal liver tissue were examined by SDS-PAGE and the bands identified at 33-34 kDa were analyzed by mass spectrometry. The prostaglandin reductase 1 (PTGR1) showed the highest number of peptides, with a confidence of level >99%. The increased expression of PTGR1 in tumors was confirmed in these two models by Western blotting and by increase in alkenal/one oxidoreductase activity (25-fold higher than normal liver). In addition, the gene expression level of Ptgr1, as measured by qRT-PCR, was increased during cancer development in a time-dependent manner (200-fold higher than normal liver). Furthermore, PTGR1 was detected in the cytoplasm of neoplastic cells in rat tumors and in 12 human HCC cases by immunohistochemistry. These analyses were performed by comparing the expression of PTGR1 to that of two well-known markers of hepatocarcinoma, Glutathione S-transferase pi 1 (GSTP1) in rats and glypican-3 in humans. The increased expression and activity of PTGR1 in liver carcinogenesis encourage further research aimed at understanding the metabolic role of PTGR1 in HCC and its potential application for human cancer diagnosis and treatment.
Instituto Nacional de Medicina Genómica, México D.F., Mexico.
Ricardo
R
Sánchez-Rodríguez
Instituto Nacional de Medicina Genómica, México D.F., Mexico; Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del IPN, México D.F., Mexico.
Julia Esperanza
JE
Torres-Mena
Instituto Nacional de Medicina Genómica, México D.F., Mexico.
Monica
M
De-la-Luz-Cruz
Instituto Nacional de Medicina Genómica, México D.F., Mexico.
Gloria Alejandra
GA
Bernal-Ramos
Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del IPN, México D.F., Mexico.
Saúl
S
Villa-Treviño
Instituto de Fisiología Celular. Universidad Nacional Autónoma de México, México D.F., Mexico.
Victoria
V
Chagoya-Hazas
Centro de Especialidades Médicas del Estado de Veracruz "Dr. Rafael Lucio", Xalapa Veracruz, México D.F., Mexico.
Luis
L
Landero-López
Instituto de Salud Pública de la Universidad Veracruzana. Veracruz, Mexico.
Rebeca
R
García-Román
Institut National de la Recherche Agronomique (INRA), UMR 1331 TOXALIM (Research Centre in Food Toxicology), Toulouse, France.
Patrick
P
Rouimi
Instituto Nacional de Medicina Genómica, México D.F., Mexico.
Luis
L
Del-Pozo-Yauner
Instituto Nacional de Medicina Genómica, México D.F., Mexico.
Jorge
J
Meléndez-Zajgla
Instituto Nacional de Medicina Genómica, México D.F., Mexico. Electronic address: jiperez@inmegen.gob.mx.
Julio Isael
JI
Pérez-Carreón
D000429:Alcohol Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D051381:Rats
D009363:Neoplasm Proteins; D000429:Alcohol Oxidoreductases; C082646:leukotriene B4 12-hydroxydehydrogenase
4-Hidroxynonenal; Alkenal/one oxidoreductase; Carcinogen detoxification enzymes; Diethylnitrosamine; Tumor marker