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Abstract
Differentiation-related gene-1, DRG1, is a metastasis suppressor gene whose expression has been shown to be dysregulated in a number of malignancies. The current study examines the expression of DRG1 in a clinical breast cohort and its association with a number of clinical pathological factors using quantitative polymerase chain reaction. Additionally, DRG1 expression is targeted in vitro using ribozyme transgene technology to explore the function of DRG1 in two human breast cancer cell lines. Low levels of DRG1 were found in patients who developed metastasis (p = 0.036) and who died of breast cancer (p = 0.0048) compared to disease free patients. Knockdown of DRG1 also resulted in significantly increased invasion and motility, but decreased matrix-adhesion in MCF7 cells. Knockdown of DRG1 seemed to have minimal impact on the cellular functions of the MDA-MB-231 breast cancer cell line causing no significant differences in cell growth, invasion, motility or matrix-adhesion. Thus, DRG1 appears to be linked to development of metastasis and death in patients who died as a result of breast cancer and may be useful as a prognostic factor as its knockdown appears to be linked with increased invasion and motility and decreased adhesion in MCF7 breast cancer cells.
Highlights
Metastasis suppressor genes are defined by their capacity to control metastatic dissemination without affecting growth of the primary tumour
Prognostic Index) was used as an indicator to assess the relationship between DRG1 transcript and predicted prognosis
The clinical data presented in this study suggests, similar to these previous studies, that high DRG1 patient transcript levels may be indicative of a better prognosis, with lower levels of DRG1 expression being associated with metastatic spread and patients who died from the disease
Summary
Metastasis suppressor genes are defined by their capacity to control metastatic dissemination without affecting growth of the primary tumour. The complexity of the metastatic process suggests that it is controlled at the genetic level via the activation and/or deactivation of multiple genes. The first of these metastasis suppressor genes was identified in 1988 [1]. Differentiation-related gene-1, DRG1, is a metastasis suppressor gene originally identified by differential display as being significantly up regulated by induction of differentiation in colon carcinoma cells in vitro [3]. The tumour suppressor p53 and von Hippel-Lindau factor have been shown to modulate DRG1 gene expression in vitro [14,15]
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