Coexpression of Smac/DIABLO and Estrogen Receptor in breast cancer

Author:

Espinosa Magali1,Lizárraga Floria2,Vázquez-Santillán Karla2,Hidalgo-Miranda Alfredo3,Piña-Sánchez Patricia4,Torres Javier5,García-Ramírez Román A.1,Maldonado Vilma2,Melendez-Zajgla Jorge1,Ceballos-Cancino Gisela1

Affiliation:

1. Instituto Nacional de Medicina Genómica, Department of Basic Research, Functional Cancer Genomics Laboratory, Mexico City, Mexico

2. Instituto Nacional de Medicina Genómica, Department of Basic Research, Epigenetic Laboratory, Mexico City, Mexico

3. Instituto Nacional de Medicina Genómica, Department of Basic Research, Cancer Genomics Laboratory, Mexico City, Mexico

4. Instituto Mexicano del Seguro Social, CMN S XXI, Oncology Research Unit, Molecular Oncology Laboratory, Mexico City, Mexico

5. Instituto Mexicano del Seguro Social, CMN S XXI, Unity of Research in Infectious Diseases, Mexico City, Mexico

Abstract

BACKGROUND: Smac/DIABLO is a proapoptotic protein deregulated in breast cancer, with a controversial role as a tumor marker, possibly due to a lack of correlative mRNA and protein analyses. OBJECTIVE: To investigate the association of Smac/DIABLO gene and protein levels with clinical variables in breast cancer patients. METHODS: Smac/DIABLO mRNA expression was analyzed by qPCR in 57 frozen tissues, whereas protein levels were assessed by immunohistochemistry in 82 paraffin-embedded tissues. Survivin mRNA levels were also measured. In vitro assays were performed to investigate possible regulators of Smac/DIABLO. RESULTS: Higher levels of Smac/DIABLO mRNA and protein were found in estrogen receptor (ER)-positive samples (p= 0.0054 and p= 0.0043, respectively) in comparison to ER-negative tumors. A negligible positive association was found between Smac/DIABLO and survivin expression. In vitro assays showed that Smac/DIABLO is not regulated by ER and, conversely, it does not participate in ER expression modulation. CONCLUSIONS: mRNA and protein levels of Smac/DIABLO were increased in ER-positive breast tumors in comparison with ER-negative samples, although the mechanism of this regulation is still unknown. Public databases showed a possible clinical relevance for this association.

Publisher

IOS Press

Subject

Cancer Research,Genetics,Oncology,General Medicine

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