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The transmembrane transporter ABCC3 participates in liver cancer progression and is a potential biomarker

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Tumor Biology

Abstract

The poor prognosis, few available treatment options, and multidrug resistance present in hepatocellular carcinoma are major problems, and new early biomarkers are needed to reduce the liver cancer death rate. ATP-binding cassette sub-family C member 3 (Abcc3) is overexpressed in different cancers and is associated with multidrug resistance and a carcinogenic stem cell phenotype. We present evidence for the first time that ABCC3 is a potential sanguine biomarker and anticancer target in hepatocellular carcinoma. Abcc3 mRNA expression was elevated in liver nodules and tumors in rat hepatocarcinogenesis model. Accordingly, the ABCC3 protein was preferentially overexpressed within the nodules and tumors during hepatocellular carcinoma progression and was secreted into the bloodstream of rat hepatocarcinogenesis model. The ABCC3 protein was expressed in human hepatoma cells and, importantly, was also present in HepG2- and Huh7-conditioned media. Furthermore, ABCC3 was overexpressed in human hepatocellular carcinoma. This report is the first to describe liver overexpression of Abcc3 during the cancer initiation, promotion, and progression periods in rat hepatocarcinogenesis model and in human hepatocellular carcinoma.

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Abbreviations

Abcc3:

ATP-binding cassette sub-family C member 3

HCC:

Hepatocellular carcinoma

ABC:

ATP-binging cassette

DEN:

Diethyl nitrosamine

2-AAF:

2-Acetylaminofluorene

GGT:

γ-Glutamyl transpeptidase

GST-p:

Glutathione S-transferase P

CSCs:

Cancer stem cells

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Acknowledgments

This work was supported by a scholarship (GCT), a grant contribution (178558) from CONACYT, and a postdoctoral scholarship, Multidisciplinary Project 3, from the SVT grant from CINVESTAV. We would like to acknowledge the animal technical support at UPEAL-CINVESTAV, including Rafael Leyva-Muñoz, Ricardo Gaxiola-Centeno, and Dr. Jorge Fernandez.

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Authors and Affiliations

  1. Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV), México D.F., Mexico

    Gabriela Carrasco-Torres, Samia Fattel-Fazenda, Guadalupe Soledad López-Alvarez, Saúl Villa-Treviño & Verónica Rocío Vásquez-Garzón

  2. Instituto de Salud Pública, Universidad Veracruzana, Veracruz, Mexico

    Rebeca García-Román

  3. Cátedra-CONACYT, Facultad de Medicina y Cirugía, Universidad Autónoma “Benito Juárez” de Oaxaca, Oaxaca de Juárez, Mexico

    Verónica Rocío Vásquez-Garzón

Authors
  1. Gabriela Carrasco-Torres
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  2. Samia Fattel-Fazenda
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  3. Guadalupe Soledad López-Alvarez
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  4. Rebeca García-Román
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  5. Saúl Villa-Treviño
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  6. Verónica Rocío Vásquez-Garzón
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Corresponding authors

Correspondence to Saúl Villa-Treviño or Verónica Rocío Vásquez-Garzón.

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Carrasco-Torres, G., Fattel-Fazenda, S., López-Alvarez, G.S. et al. The transmembrane transporter ABCC3 participates in liver cancer progression and is a potential biomarker. Tumor Biol. 37, 2007–2014 (2016). https://doi.org/10.1007/s13277-015-3999-5

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  • DOI: https://doi.org/10.1007/s13277-015-3999-5

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