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Alteration of pro‐apoptotic and anti‐apoptotic gene expression in breast cancer cell lines (1047.7)
Author(s) -
Edson Leanne,
Hunter Dylan,
Coleman William
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1047.7
Subject(s) - demethylating agent , gene silencing , dna methylation , cancer research , biology , cancer cell , epigenetics , cancer , apoptosis , microbiology and biotechnology , gene expression , gene , genetics
A subset of human triple‐negative breast cancer cell lines exhibit aberrant DNA hypermethylation that is associated with DNA methyltransferase hyperactivity, overexpression of DNMT3b, and methylation‐dependent silencing of numerous genes. These breast cancer cell lines are resistant to standard chemotherapeutic agents, but can be sensitized to chemotherapy with demethylating drugs (5aza). In this study, we surveyed expression of 328 genes associated with apoptosis and survival in Hs578T cells using BioRad Prime PCR Pathway Plates. This analysis identified several pro‐apoptotic genes that are not expressed (undetected) or expressed at negligible levels in Hs578T cells, including FASLG, IGF1, CD27, and BIK. Epigenetic silencing of these genes (directly or indirectly) would convey a survival advantage to the cancer cells through elimination of pro‐apoptotic signaling. These pro‐apoptotic genes and/or members of their pathways have been shown to be subject to methylation‐dependent silencing in cancer cells. In addition, several anti‐apoptotic genes were found to be abundantly expressed in Hs578T cells, including HSPB1 and NPM1. It is not known if epigenetic mechanisms contribute to overexpression of anti‐apoptotic genes in breast cancer. The contributions of aberrant DNA hypermethylation to the silencing of pro‐apoptotic genes (and/or activation of anti‐apoptotic genes) as a mechanism of chemotherapeutic resistance was explored further using a panel of breast cancer cell lines. The results suggest that treatment of triple‐negative breast cancer cell lines that display aberrant DNA hypermethylation with demethylating agents (like 5aza) sensitizes them to standard chemotherapeutic drugs (Doxorubicin, Paclitaxel, 5‐fluorouracil) by reactivation of pro‐apoptotic genes. This experimental observation forms the basis for designing new treatment approaches for patients with triple‐negative breast cancer that combine epigenetic and cytotoxic drugs.