Affiliations: [a] Instituto Nacional de Medicina Genómica, Department of Basic Research, Functional Cancer Genomics Laboratory, Mexico City, Mexico | [b] Instituto Nacional de Medicina Genómica, Department of Basic Research, Epigenetic Laboratory, Mexico City, Mexico | [c] Instituto Nacional de Medicina Genómica, Department of Basic Research, Cancer Genomics Laboratory, Mexico City, Mexico | [d] Instituto Mexicano del Seguro Social, CMN S XXI, Oncology Research Unit, Molecular Oncology Laboratory, Mexico City, Mexico | [e] Instituto Mexicano del Seguro Social, CMN S XXI, Unity of Research in Infectious Diseases, Mexico City, Mexico
Correspondence:
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Corresponding author: Gisela Ceballos-Cancino, Instituto Nacional de Medicina Genómica, Department of Basic Research, Functional Cancer Genomics Laboratory, Periférico Sur 4809, Col. Arenal Tepepan, Tlalpan 14610, Mexico. Tel.: +52 55 5350 1967; E-mail: [email protected].
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.
Keywords: Smac/DIABLO, survivin, breast cancer, estrogen receptor
