We have established gene expression patterns of renal cell carcinomas using DNA microarrays in order to identify genes relevant of the tumour biology and clinical course of this disease. The von Hippel Lindau tumour suppressor is mutated in clear cell renal carcinoma, which leads to constitutive activation of hypoxia inducible factor (HIF) transcription factors and to expression of its target genes. We found that Activin B, a member of the TGFb family is highly over expressed in kidney tumours as compared to normal kidneys. Furthermore, expression of Activin B is stimulated by hypoxia via HIFs and repressed by VHL. Functional studies showed that Activin B reduces adhesion of RCC cells to extracelllular matrix and promotes invasion of tumour cells in vitro. Importantly, knock-down of Activin B inhibited tumour growth of kidney tumour cells in nude mice. Collectively, the data show that the loss of Activin B has similar consequences as the reconstitution of wildtype VHL in kidney tumour cells. Our results indicate that Activin B is a major oncogenic factor in kidney tumours.