Abstract 3842: Expression analysis of SMYD5 in breast cancer and normal tissues

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Lysine methyltransferases are a group of enzymes that carry a SET domain, which catalyzes the addition of methyl groups to specific lysine residues. Several lysine methyltransferases have been described to be involved in human carcinogenesis. The SMYD family of methyltransferases constitutes a group of five genes that encodes proteins bearing a SET and a MYND domain, whose activity have not yet been completely characterized. Although deregulation of SMYD family members has been reported to contribute to cancer progression through several different mechanisms, to date a clear relationship of SMYD5 with breast cancer, the second most frequent cancer worldwide and the most common among women, was not determined. In the present study we investigated the expression profile of SMYD5 in breast tumors and adjacent non-tumor samples, in breast cancer cell lines and in several normal tissues. qPCR revealed SMYD5 mRNA expression level was downregulated in 7 breast cancer cell lines when compared to normal breast tissues. Relative expression of SMYD5 in breast tumors and normal breast samples revealed a significant (p<0.001) reduction of SMYD5 expression in tumors comparing to the non-cancerous breast samples. These findings led us to investigate the role of SMYD5 in cell proliferation. We observed that reduction of SMYD5 expression by shRNA in HEK293 cells induced acceleration in culture growth. Moreover, the generation of MDA-MB-231 tumor sublines expressing varying levels of SMYD5 revealed different proliferative profiles. SMYD5 expression inversely correlated with growth rate in highly proliferative cultures. However, slow proliferating cells (i.e. long doubling time) do not seem to be affected by SMYD5 levels. This observation indicates that specific subgroup of highly proliferative cells may depend on SMYD5 downregulation to exhibit this phenotype. In addition, we found that SMYD5 has a sub-cellular distribution similar to other SMYD family proteins suggesting it may exert enzymatic activity in both cytosolic and nuclear substrates. Taken together, our data indicates a possible role for SMYD5 in modulating breast carcinogenesis through epigenetic alterations, probably acting as tumor suppressor. Note: This abstract was not presented at the meeting. Citation Format: Joao Nunes de Matos Neto, Maira de Azevedo Feitosa Araujo, Doralina do Amaral Rabello, Andrea Barretto Motoyama, Diego Madureira de Oliveira, Fabio Pittella Silva. Expression analysis of SMYD5 in breast cancer and normal tissues. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3842. doi:10.1158/1538-7445.AM2015-3842