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Introduction The malignant growth of cancer is fueled in part by pathological alterations of the genome that reconfigure the transcriptional programming of cells. This transcriptional restructuring gives rise to the [...], Aggressive forms of cancer are often defined by recurrent chromosomal alterations, yet in most cases, the causal or contributing genetic components remain poorly understood. Here, we utilized microarray informatics to identify candidate oncogenes potentially contributing to aggressive breast cancer behavior. We identified the Rab-coupling protein RCP (also known as RAB11FIP1), which is located at a chromosomal region frequently amplified in breast cancer (8p11-12) as a potential candidate. Overexpression of RCP in MCF10A normal human mammary epithelial cells resulted in acquisition of tumorigenic properties such as loss of contact inhibition, growth-factor independence, and anchorage-independent growth. Conversely, knockdown of RCP in human breast cancer cell lines inhibited colony formation, invasion, and migration in vitro and markedly reduced tumor formation and metastasis in mouse xenograft models. Overexpression of RCP enhanced ERK phosphorylation and increased Ras activation in vitro. As these results indicate that RCP is a multifunctional gene frequently amplified in breast cancer that encodes a protein with Ras-activating function, we suggest it has potential importance as a therapeutic target. Furthermore, these studies provide new insight into the emerging role of the Rab family of small G proteins and their interacting partners in carcinogenesis.

Background: The binding events of DNA-interacting proteins and their patterns can be extensively characterized by high density ChIP-chip tiling array data. The characteristics of the binding events could be different for different transcription factors. They may even vary for a given transcription factor among different interaction loci. The knowledge of binding sites and binding occupancy patterns are all very useful to understand the DNA-protein interaction and its role in the transcriptional regulation of genes. Results: In the view of the complexity of the DNA-protein interaction and the opportunity offered by high density tiled ChIP-chip data, we present a statistical procedure which focuses on identifying the interaction signal regions instead of signal peaks using moving window binomial testing method and deconvolving the patterns of interaction using peakedness and skewness scores. We analyzed ChIP-chip data of 4 different DNA interacting proteins including transcription factors and RNA polymerase in fission yeast using our procedure. Our analysis revealed the variation of binding patterns within and across different DNA interacting proteins. We present their utility in understanding transcriptional regulation from ChIP-chip data. Conclusions: Our method can successfully detect the signal regions and characterize the binding patterns in ChIPchip data which help appropriate analysis of the ChIP-chip data. [ABSTRACT FROM AUTHOR]

Aggressive forms of cancer are often defined by recurrent chromosomal alterations, yet in most cases, the causal or contributing genetic components remain poorly understood. Here, we utilized microarray informatics to identify candidate oncogenes potentially contributing to aggressive breast cancer behavior. We identified the Rab-coupling protein RCP (also known as RAB11FIP1), which is located at a chromosomal region frequently amplified in breast cancer (8p11-12) as a potential candidate. Overexpression of RCP in MCF10A normal human mammary epithelial cells resulted in acquisition of tumorigenic properties such as loss of contact inhibition, growth-factor independence, and anchorage-independent growth. Conversely, knockdown of RCP in human breast cancer cell lines inhibited colony formation, invasion, and migration in vitro and markedly reduced tumor formation and metastasis in mouse xenograft models. Overexpression of RCP enhanced ERK phosphorylation and increased Ras activation in vitro. As these results indicate that RCP is a multifunctional gene frequently amplified in breast cancer that encodes a protein with Ras-activating function, we suggest it has potential importance as a therapeutic target. Furthermore, these studies provide new insight into the emerging role of the Rab family of small G proteins and their interacting partners in carcinogenesis. [ABSTRACT FROM AUTHOR]