Project description:In advanced malignancies, cancer cells have acquired capabilities to resist a variety of stress-inducing insults. We show that c-Jun N-terminal kinase (JNK) stress signaling is highly active in cancer cells from patients with late stage breast cancer and promotes tumor growth and metastasis in mouse models. Transcriptomic analysis revealed that JNK activity induces genes associated with extracellular matrix (ECM), wound healing and mammary stem cells. The ECM proteins and niche components osteopontin (SPP1) and tenascin C (TNC) are induced by JNK signaling and promote metastatic colonization of the lungs. Notably, treatment with chemotherapeutic drugs induces JNK activity in breast cancer cells, reinforcing the production of SPP1 and TNC. Inhibition of JNK or reduction of SPP1 or TNC expression sensitizes primary tumors and metastases in mice to chemotherapy. We used Affymetrix microarrays to analyze the transcriptomic output modulated by JNK activity in a lung metastatic derivative of the MDA-MB-231 breast cancer cell line, MDA231-LM2.
Project description:In advanced malignancies, cancer cells have acquired capabilities to resist a variety of stress-inducing insults. We show that c-Jun N-terminal kinase (JNK) stress signaling is highly active in cancer cells from patients with late stage breast cancer and promotes tumor growth and metastasis in mouse models. Transcriptomic analysis revealed that JNK activity induces genes associated with extracellular matrix (ECM), wound healing and mammary stem cells. The ECM proteins and niche components osteopontin (SPP1) and tenascin C (TNC) are induced by JNK signaling and promote metastatic colonization of the lungs. Notably, treatment with chemotherapeutic drugs induces JNK activity in breast cancer cells, reinforcing the production of SPP1 and TNC. Inhibition of JNK or reduction of SPP1 or TNC expression sensitizes primary tumors and metastases in mice to chemotherapy. In order to investigate cancer cell-response to chemotherapy, we exposed MDA231-LM2 breast cancer cells to the chemotherapeutic agent paclitaxel and performed transcriptomic analysis using Affymetrix microarray.
Project description:Purpose: To identify downstream signaling pathways that mediate functions of GALNT14 Methods: RNAs isolated from MDA231-LM2 cells expressing shCntr or shGALNT14 and MDA231-Par cells expressing pBabe-Hygro control vector or GALNT14 expression vector were analyzed by using an Illumina HiSeq 2500 Conclusions: Our study represents the first transcriptome profile of GALNT14-depleted MDA231-LM2 and GALNT14-overexpressing Par cells.
Project description:Metastasis is the main cause of mortality of breast cancer. To explore the mechanisms of arsenic trioxide (ATO) in inhibition of breast cancer metastasis, ATO regulated genes in breast cancer MDA-MB-231 and LM2-4175 cells were studied. After data analysis, ATO regulated genes were involved in TP53, TGFβ and TNFα signaling pathways. Furthermore, TGFβ and TNFα activated genes in breast cancer MDA-MB-231 cells were studied.