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Differential Expression of Ion Channels and Transporters During Hepatocellular Carcinoma Development

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Abstract

Background

Ion channels and transporters are potential markers and therapeutic targets for several cancers. However, their expression during hepatocellular carcinoma (HCC) development remains unclear.

Aim

To investigate the mRNA expression of Na+, K+ and Ca2+ channels and ABC transporters during rat HCC development, as well as Abcc3 protein in human liver biopsies.

Methods

Wistar rats were treated with diethylnitrosamine (DEN) and developed both cirrhosis (12 weeks of treatment) and either pre-neoplastic lesions (16 weeks of treatment) or multinodular HCC (16 weeks of treatment plus 2 weeks DEN-free). The mRNA expression of 12 ion channels and two ABC transporters was studied using real-time RT-PCR. Tumor-containing or tumor-free liver sections were isolated by laser-capture microdissection. Abcc3 protein expression was studied by immunohistochemistry in healthy, cirrhotic and HCC human biopsies.

Results

We observed expression changes in seven genes. Kcna3, Kcnn4, Kcnrg and Kcnj11 potassium channel mRNA expression reached peak values at the end of DEN treatment, while Scn2a1 sodium channel, Trpc6 calcium channel and Abcc3 transporter mRNA expression reached their highest levels in the presence of HCC (18 weeks). Whereas Kcnn4 and Scn2a1 channel expression was similar in non-tumor and tumor tissue, the Abcc3 transporter and Kcna3 potassium channels were preferentially overexpressed in the tumor sections. We observed differential Abcc3 protein subcellular localization and expression in human samples.

Conclusions

The ion channel/transporter expression profile observed suggests that these genes are potential early markers or therapeutic targets of HCC. The differential localization of Abcc3 may be useful in the diagnosis of cirrhosis and HCC.

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Acknowledgments

We thank Eduardo García Osornio, M.V.Z. Ricardo Gaxiola and Rafael Leyva for their technical assistance. This work was partially supported by the Consejo Nacional de Ciencia y Tecnología grant 168102 to JC and grant 115431 to JIP-C.

Ethical approval

All applicable international, national and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This is a retrospective study, and for this type of study, formal consent is not required.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Pharmacology, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, Avenida Instituto Politécnico Nacional 2508, C.P. 07360, Mexico City, Mexico

    Violeta Zúñiga-García, María de Guadalupe Chávez-López, Elisabeth Hernández-Gallegos & Javier Camacho

  2. Instituto Nacional de Medicina Genómica, Periférico Sur No. 4809, Col. Arenal Tepepan, 14610, Mexico City, Mexico

    Valeria Quintanar-Jurado, Nayeli Belem Gabiño-López & Julio Isael Pérez-Carreón

  3. Departamento de Patología, Hospital General de México, Mexico City, Mexico

    Juan Soriano-Rosas

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  1. Violeta Zúñiga-García
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  2. María de Guadalupe Chávez-López
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  3. Valeria Quintanar-Jurado
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Corresponding author

Correspondence to Javier Camacho.

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Zúñiga-García, V., Chávez-López, M.d.G., Quintanar-Jurado, V. et al. Differential Expression of Ion Channels and Transporters During Hepatocellular Carcinoma Development. Dig Dis Sci 60, 2373–2383 (2015). https://doi.org/10.1007/s10620-015-3633-9

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  • DOI: https://doi.org/10.1007/s10620-015-3633-9

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