Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Naa10p's effect on gene expression profiles in MCF7 breast cancer cells

ABSTRACT: N-?-acetyltransferase 10 protein (Naa10p, also called ARD1), the catalytic subunit of N-acetyltransferase A, is a critical regulator of cell death and proliferation. Naa10p is also shown to regulate cancer metastasis by inhibiting cell motility, however its role in cancer metastasis is not fully understood. In this study, we found that high expression of Naa10p is positively correlated with the survival of patients with breast cancer, while negatively correlated with lymph node metastasisr. Naa10p inhibits breast cancer cell migration and invasion in vitro and decreases the xenograft growth and metastasis in nude mice. Microarray screening revealed that Naa10p down-regulates expression of several pro-invasive genes, which was validated by qRT-PCR analysis. To gain an insight into Naa10p’s inhibitory effect on cancer metastasis, we performed microarray analysis with RNA samples extracted from Naa10p-silenced MCF-7 (MCF-7SA) and control cells (MCF-7NC).

ORGANISM(S): Homo sapiens

SUBMITTER: Like Qu

PROVIDER: E-GEOD-52723 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

Inhibition of STAT5a by Naa10p contributes to decreased breast cancer metastasis.

Zeng Yan Y Min Li L Han Yong Y Meng Lin L Liu Caiyun C Xie Yuntao Y Dong Bin B Wang Lixin L Jiang Beihai B Xu Huiyu H Zhuang Qing Q Zhao Chuanke C Qu Like L Shou Chengchao C

Carcinogenesis 20140612 10

N-α-Acetyltransferase 10 protein (Naa10p, also called arrest-defective 1), the catalytic subunit of N-acetyltransferase A, is a critical regulator of cell death and proliferation. Naa10p is also shown to regulate cancer metastasis by inhibiting cell motility; however, its role in cancer metastasis is not fully understood. In this study, we found that high expression of Naa10p is positively correlated with the survival of patients with breast cancer, whereas negatively correlated with lymph node ...[more]

PMID: 24925029

Similar Datasets

Project description:Multiple gene expression studies have demonstrated that breast cancer biological diversity is associated with distinct transcriptional programs. Transcription factors, because of their unique ability to coordinate the expression of multiple genes, are speculated to play a role in generating phenotypic plasticity associated with cancer progression including acquired drug resistance. Combinatorial libraries of artificial zinc-finger transcription factors (ZF-TFs) provide a robust means for inducing and understanding various functional components of the cancer phenotype. Herein, we utilized combinatorial ZF-TF library technology to better understand how breast cancer cells acquire resistance to a fulvestrant, a clinically important anti-endocrine therapeutic agent. We isolated six ZF-TF library members capable of inducing stable, long-term anti-endocrine drug-resistance in two independent estrogen receptor positive breast cancer cell lines. Comparative gene expression profile analysis of the ZF-TF-transduced breast cancer cell lines revealed a 72-gene cluster that constituted a common signature for the fulvestrant-resistance phenotype. Pathway enrichment-analysis of gene expression data revealed that the ZF-TF-induced fulvestrant resistance is associated with an estrogen receptor negative-like gene set and four unique myb-regulated gene sets. Furthermore, we identified a set of genes strongly expressed in the ZF-TF-induced fulvestrant-resistant cells that was correlated with a lower probability of distant metastasis-free or death-from-relapse-free survival of breast cancer patients. MCF7-R73 cells, a monoclonal MCF7 subline that is highly sensitive to fulvestrant-induced cytocidal activity, underwent retroviral transduction with the zinc finger transcription factor (ZF-TF) activator library or with a control plasmid encoding only the NF-kB p65 activation domain. Both populations of cells were enriched for transduced cells by selecting for growth in puromycin and for fulvestrant-resistant cells by selecting with 100 nM fulvestrant. After 6 weeks of continuous treatment with fulvestrant, hundreds of drug-resistant colonies emerged from the population of cells infected with the ZF-TF activator library. By contrast, as expected, the control MCF7cell line transduced by NF-kB p65-only underwent massive cell death resulting in the complete absence of resistant colonies. DNA encoding the zinc-finger arrays was rescued by PCR from genomic DNA of pooled fulvestrant-resistant cells. The sequences of the ZF-TFs were determined and 46 unique ZF-TF clones identified. These 46 unique ZF-TFs were re-cloned into the retroviral vector and converted into clonal virus stocks that were used to transduce MCF7-R73 cells. These 46 retrovirally transduced cell populations were then challenged with fulvestrant. As compared with the control MCF-238 cells, MCF7-R73 cells transduced with six unique ZF-TFs demonstrated survival and growth in the presence of 100nM fulvestrant.

Dataset Information

Naa10p's effect on gene expression profiles in MCF7 breast cancer cells

Publications

Inhibition of STAT5a by Naa10p contributes to decreased breast cancer metastasis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure