Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Infinium HumanMethylation450 BeadChip Array analysis of human breast cancer cell line MDA-MB-231

ABSTRACT: Breast cancer metastasis may occur rapidly after tumor development and is responsible for the high mortality rate of this disease. ITIH5 has been shown being lost in tumor progression of various cancer types including breast cancer. Its dysfunction was associated with poor prognosis, while mechanisms of ITIH5 biology are still unrevealed. ITIH5 promoter methylation and expression was analyzed using an Infinium HumanMethylation450 BeadChip Array and Affymetrix 1.0 ST gene array, respectively, to identify ITIH5-associated gene signatures and signaling pathways. MDA-MB-231 cells were transfected with ITIH5-pBK-CMV expression vector, containing the full-length human ITIH5 cDNA derived from normal breast tissue, or the empty vector. Single-cell clones were selected by limited dilution under geneticine (G418) pressure. We compared the transcriptomic and epigenomic profile of wildtype MDA-MB-231 cells, mock clones without ITIH5 expression (clone 1 and 2) and ÎpBK-ITIH5 clones (clone 4, 7 and 12). Related transcription profiling data are found under accession E-MTAB-1813.

ORGANISM(S): Homo sapiens

SUBMITTER: Michael Rose

PROVIDER: E-MTAB-5081 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Since bone metastatic breast cancer is an incurable disease, causing significant morbidity and mortality, understanding of the underlying molecular mechanisms would be highly valuable. Here, we describe in vitro and in vivo evidence for the importance of serine biosynthesis in the metastasis of breast cancer to bone. We first characterized the bone metastatic propensity of the MDA-MB-231(SA) cell line variant as compared to the parental MDA-MB-231 cells by radiographic and histological observations in the inoculated mice. Genome-wide gene expression profiling of this isogenic cell line pair revealed that all the three genes involved in the L-serine biosynthesis pathway, phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), and phosphoserine phosphatase (PSPH) were upregulated in the highly metastatic variant. This pathway is the primary endogenous source for L-serine in mammalian tissues. Consistently, we observed that the proliferation of MDA-MB-231(SA) cells in serine-free conditions was dependent on PSAT1 expression. In addition, we observed that L-serine is essential for the formation of bone resorbing human osteoclasts and may thus contribute to the vicious cycle of osteolytic bone metastasis. High expression of PHGDH and PSAT1 in primary breast cancer was significantly associated with decreased relapse-free and overall survival of patients and malignant phenotypic features of breast cancer. In conclusion, high expression of serine biosynthesis genes in metastatic breast cancer cells and the stimulating effect of L-serine on osteoclastogenesis and cancer cell proliferation indicate a functionally critical role for serine biosynthesis in bone metastatic breast cancer and thereby an opportunity for targeted therapeutic interventions. Parental MDA-MB-231 cells and MDA-MB-231(SA) cells were cultured in cell culture flasks. RNA was isolated in order to compare the gene expression profiles of these cell variants. Total of two samples. No replicates.

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Infinium HumanMethylation450 BeadChip Array analysis of human breast cancer cell line MDA-MB-231

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