Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human MDA-MB-231 cells infeted with Flag-SR-IkBa vs. vector

ABSTRACT: We used human Affymetrix microarrays to identify the up- or down-regulated gene expressions from MDA-MB-231 cells infected with control vector or Flag-SR-IkBa Experiment Overall Design: The pattern of gene expression from MDA-MB-231 cells transduced with retroviruses were analysed by RNA extraction and hybridization on Affymetrix microarrays. From expression profiles, we identified NF-kB target genes, and uncovered a novel and specific role of a gene in osteolytic bone metastasis.

ORGANISM(S): Homo sapiens

SUBMITTER: Bae Keun Park

PROVIDER: E-GEOD-6324 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

NF-kappaB in breast cancer cells promotes osteolytic bone metastasis by inducing osteoclastogenesis via GM-CSF.

Park Bae Keun BK Zhang Honglai H Zeng Qinghua Q Dai Jinlu J Keller Evan T ET Giordano Thomas T Gu Keni K Shah Veena V Pei Lei L Zarbo Richard J RJ McCauley Laurie L Shi Songtao S Chen Shaoqiong S Wang Cun-Yu CY

Nature medicine 20061210 1

Advanced breast cancers frequently metastasize to bone, resulting in osteolytic lesions, yet the underlying mechanisms are poorly understood. Here we report that nuclear factor-kappaB (NF-kappaB) plays a crucial role in the osteolytic bone metastasis of breast cancer by stimulating osteoclastogenesis. Using an in vivo bone metastasis model, we found that constitutive NF-kappaB activity in breast cancer cells is crucial for the bone resorption characteristic of osteolytic bone metastasis. We iden ...[more]

PMID: 17159986

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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.

Dataset Information

Transcription profiling of human MDA-MB-231 cells infeted with Flag-SR-IkBa vs. vector

Publications

NF-kappaB in breast cancer cells promotes osteolytic bone metastasis by inducing osteoclastogenesis via GM-CSF.

Similar Datasets

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