5071

We had previously defined by allele loss studies a minimal region at 6q27 (between D6S264 and D6S297) to contain a putative tumour suppressor gene. The p90 Ribosomal S6 kinase-3 gene (p90 Rsk-3, RPS6KA2) maps in this interval. It is a serine-threonine kinase that signals downstream of the MAPK pathway. It is expressed in normal ovarian epithelium, whilst reduced or absent in tumours or cell lines. We show that RPS6KA2 is monoallelically expressed in the ovary suggesting that loss of a single expressed allele is sufficient to cause complete loss of expression in cancer cells. Further, we have identified two new isoforms of RPS6KA2 with an alternative start codon. Homozygous deletions were identified within the RPS6KS2 gene in two cell lines. Re-expression of RPS6KA2 in ovarian cancer cell lines suppressed colony formation, reduced proliferation, caused G1 arrest and increased apoptosis. This suggests that RPS6KA2 is a putative tumour suppressor gene involved in the pathogenesis of ovarian cancer.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA