Transcriptomics

Dataset Information

20

Expression data from MDA-MB-231 parental and xenograft tumor cells treated with Smac mimetic SM-164.


ABSTRACT: Small-molecule Smac mimetics target inhibitor of apoptosis (IAP) proteins to induce TNFα-dependent apoptosis in cancer cells and several Smac mimetics have been advanced into clinical development as a new class of anticancer drugs. However, preclinical studies have shown that only a small subset of cancer cell lines are sensitive to Smac mimetics used as single agents and these cell lines are at risk of developing drug resistance to Smac mimetics. Thus, it is important to understand the molecular mechanisms underlying intrinsic and acquired resistance of cancer cells to Smac mimetics in order to develop effective therapeutic strategies to overcome or prevent Smac mimetic resistance. We established Smac mimetic resistant sublines derived from MDA-MB-231 breast cancer cells, which exhibit exquisite sensitivity to the Smac mimetic SM-164, and used microarrays to detail the global programme of gene expression underlying SM-164 resistance in MDA-MB-231 cells and identified differentially expressed genes in SM-164-resistant and -sensitive MDA-MB-231 cells. SCID mice with MDA-MB-231 xenograft tumors were treated with 5 mg/kg of SM-164 intravenously for 5 days/week for 2 weeks. SM-164-regressed MDA-MB-231 tumors regrew after treatment ended. Tumor cells from these regrown MDA-MB-231 tumors were isolated and total RNAs were prepared for microarray analysis.

REANALYSED by: E-GEOD-33827

ORGANISM(S): Homo sapiens  

SUBMITTER: Longchuan Bai   Shaomeng Wang 

PROVIDER: E-GEOD-33827 | ArrayExpress | 2012-03-01

SECONDARY ACCESSION(S): GSE33827PRJNA148199

REPOSITORIES: GEO, ArrayExpress

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Publications

LRIG1 modulates cancer cell sensitivity to Smac mimetics by regulating TNFα expression and receptor tyrosine kinase signaling.

Bai Longchuan L   McEachern Donna D   Yang Chao-Yie CY   Lu Jianfeng J   Sun Haiying H   Wang Shaomeng S  

Cancer research 20120112 5


Smac mimetics block inhibitor of apoptosis proteins to trigger TNFα-dependent apoptosis in cancer cells. However, only a small subset of cancer cells seem to be sensitive to Smac mimetics and even sensitive cells can develop resistance. Herein, we elucidated mechanisms underlying the intrinsic and acquired resistance of cancer cells to Smac mimetics. In vitro and in vivo investigations revealed that the expression of the cell surface protein LRIG1, a negative regulator of receptor tyrosine kinas  ...[more]

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