Deregulated expression of LRBA facilitates cancer cell growth

LRBA expression is induced by mitogens in lymphoid and myeloid cells. The Drosophila LRBA orthologue rugose/DAKAP550 is involved in Notch, Ras and EGFR pathways. These findings suggest that LRBA could play a role in cell types that have increased proliferative and survival capacity. Here, we show by...

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Bibliographic Details
Published in:	Oncogene Vol. 23; no. 23; pp. 4089 - 4097
Main Authors:	WANG, Jia-Wang, GAMSBY, Joshua J, JIANDONG CHEN, KERR, William G, HIGHFILL, Steven L, MORA, Linda B, BLOOM, Gregory C, YEATMAN, Tim J, PAN, Tien-Chi, RAMNE, Anna L, CHODOSH, Lewis A, CRESS, W. Douglas
Format:	Journal Article
Language:	English
Published:	Basingstoke Nature Publishing 20-05-2004 Nature Publishing Group
Subjects:	Adaptor Proteins, Signal Transducing Base Sequence Biological and medical sciences Breast Neoplasms - metabolism Cancer Carrier Proteins - genetics Carrier Proteins - metabolism Cell Cycle Proteins Cell growth Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Cyclic AMP-Dependent Protein Kinases - genetics Cyclic AMP-Dependent Protein Kinases - metabolism DNA-Binding Proteins - metabolism E2F Transcription Factors E2F1 Transcription Factor Epidermal growth factor receptors Estrogens Female Fundamental and applied biological sciences. Psychology Genes Growth inhibition HeLa Cells Humans Insects Kinases Medical research Mitogens Molecular and cellular biology Molecular Sequence Data mRNA Mutants Mutation Myeloid cells Neoplasms - metabolism Oncology Phosphorylation Promoter Regions, Genetic Proteins Receptors, Estrogen - metabolism RNA Interference - physiology RNA-mediated interference Transcription Factors - metabolism Tumor necrosis factor-TNF Tumors United States > US Gene silencing TP53 Gene RNA interference Growth LRBA E2F Malignant tumor Gene expression gene expression profiling Carcinogenesis Tumor suppressor gene P53
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Summary:	LRBA expression is induced by mitogens in lymphoid and myeloid cells. The Drosophila LRBA orthologue rugose/DAKAP550 is involved in Notch, Ras and EGFR pathways. These findings suggest that LRBA could play a role in cell types that have increased proliferative and survival capacity. Here, we show by microarray and real-time PCR analyses that LRBA is overexpressed in several different cancers relative to their normal tissue controls. We also show that LRBA promoter activity and endogenous LRBA mRNA levels are reduced by p53 and increased by E2F1, indicating that mutations in the tumor suppressors p53 and Rb could contribute to the deregulation of LRBA. Furthermore, inhibition of LRBA expression by RNA interference, or inhibition of its function by a dominant-negative mutant, leads to significant growth inhibition of cancer cells, demonstrating that deregulated expression of LRBA contributes to the altered growth properties of a cancer cell. Finally, we show that the phosphorylation of EGFR is affected by the dominant-negative mutant, suggesting LRBA plays a role in the mammalian EGFR pathway. These findings demonstrate that LRBA facilitates cancer cell growth and thus LRBA may represent a novel molecular target for cancer therapy.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0950-9232 1476-5594
DOI:	10.1038/sj.onc.1207567