TNF-alpha gene signature in triple-negative breast cancer cells
Triple-negative breast cancer patients have an increased likelihood of distant recurrence and death when compared with patients with other subtypes of breast cancer. High persistence of tumor necrosis factor-alpha (TNFα) in breast tumors is linked with local recurrence and new metastasis. TNFα stimulates the RAS-mitogen activated protein kinase and stress kinase pathways; both of which activate the mitogen- and stress-activated protein kinases. We hypothesized that mitogen- and stress-activated protein kinases have a role in the TNFα-response gene signature in triple-negative breast cancer cells. MDA-MB-231 cells were used to determine the TNFα gene signature in triple-negative breast cancers. RNA-sequencing data revealed that immediate early genes involved in carcinogenesis were strongly induced. Validation studies with the mitogen- and stress-activated protein kinase inhibitor H89 attenuated the induction of these genes, suggesting these kinases play a role in their induction and subsequently may be a potential therapeutic target for triple-negative breast cancers.