Loss of expression of growth differentiation factor-9 (GDF9) in human kidney cancer and regulation of growth and migration of kidney cancer cells by GDF9.

BACKGROUND Growth differentiation factor-9 (GDF9), a member of the bone morphogenetic protein (BMP) family and the transforming growth factor (TGF)-beta superfamily, has recently been implicated in the biological control of cancer cell behaviour. It has also been implicated in the development and spread of solid cancer. However, the role of GDF9 in kidney cancer remains to be investigated. In the present study, the expression of GDF9 in normal and malignant human kidney tissues and its molecular and cellular impact on human kidney cancer cells were investigated. MATERIALS AND METHODS The expression of GDF9 in human kidney tissues and kidney cancer cell lines (UMRC-2 and CAKI-2) was assessed at both the mRNA and protein levels using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively. GDF9 overexpression was induced by a mammalian GDF9 expression construct. The effect of GDF9 expression on cellular functions was examined in kidney cancer cells overexpressing GDF9 using a variety of in vitro assays. RESULTS In normal kidney tissues, stronger staining of GDF9 was seen in renal tubular epithelial cells, both in the cytoplasm and in the nucleus. In contrast, the staining of GDF9 was notably weak or absent in cells of tumour tissues. Human kidney cancer cell lines UMRC-2 and CAKI-2 had lost their GDG-9 expression. Overexpression of GDF9 reduced in vitro invasion and cellular growth and migration of kidney cell lines in vitro. Using the electric cell-substrate sensing (ECIS) method, it was further revealed that overexpression of GDF9 in these cells markedly reduced cellular migration and adhesion. CONCLUSION Human kidney tumours have a reduced or loss of expression of GDF9. In vitro, GDF9 overexpression suppresses the invasiveness, growth and migration of kidney cancer cells. This suggests that GDF9 is a potential tumour suppressor and may have prognostic and therapeutic implications in human kidney cancer.