Research Papers:

Reprogramming human A375 amelanotic melanoma cells by catalase overexpression: Upregulation of antioxidant genes correlates with regression of melanoma malignancy and with malignant progression when downregulated

Candelaria Bracalente, Irene L. Ibañez, Ariel Berenstein, Cintia Notcovich, María B. Cerda, Fabio Klamt, Ariel Chernomoretz and Hebe Durán _

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Oncotarget. 2016; 7:41154-41171. https://doi.org/10.18632/oncotarget.9273

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Candelaria Bracalente1,2,*, Irene L. Ibañez1,2,*, Ariel Berenstein3, Cintia Notcovich1, María B. Cerda1, Fabio Klamt4, Ariel Chernomoretz3, Hebe Durán1,2,5

1Departamento de Micro y Nanotecnología, Comisión Nacional de Energía Atómica, San Martín, Buenos Aires, Argentina

2Consejo Nacional de Investigaciones Científicas y Tecnológicas, Buenos Aires, Argentina

3Fundación Instituto Leloir and Departamento de Física, Facultad Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina

4Laboratório de Bioquímica Celular, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brasil

5Escuela de Ciencia y Tecnología, Universidad Nacional de San Martín, San Martín, Buenos Aires, Argentina

*These authors contributed equally to this work

Correspondence to:

Hebe Durán, email: hduran@cnea.gov.ar

Keywords: melanoma, AOS network, melanogenesis, metastasis, microarrays

Received: October 28, 2015     Accepted: April 02, 2016     Published: May 10, 2016


Reactive oxygen species (ROS) are implicated in tumor transformation. The antioxidant system (AOS) protects cells from ROS damage. However, it is also hijacked by cancers cells to proliferate within the tumor. Thus, identifying proteins altered by redox imbalance in cancer cells is an attractive prognostic and therapeutic tool. Gene expression microarrays in A375 melanoma cells with different ROS levels after overexpressing catalase were performed. Dissimilar phenotypes by differential compensation to hydrogen peroxide scavenging were generated. The melanotic A375-A7 (A7) upregulated TYRP1, CNTN1 and UCHL1 promoting melanogenesis. The metastatic A375-G10 (G10) downregulated MTSS1 and TIAM1, proteins absent in metastasis. Moreover, differential coexpression of AOS genes (EPHX2, GSTM3, MGST1, MSRA, TXNRD3, MGST3 and GSR) was found in A7 and G10. Their increase in A7 improved its AOS ability and therefore, oxidative stress response, resembling less aggressive tumor cells. Meanwhile, their decrease in G10 revealed a disruption in the AOS and therefore, enhanced its metastatic capacity.

These gene signatures, not only bring new insights into the physiopathology of melanoma, but also could be relevant in clinical prognostic to classify between non aggressive and metastatic melanomas.

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