Amplification and overexpression of PRUNE in human sarcomas and breast carcinomas - a possible mechanism for altering the nm23-H1 activity

PRUNE, the human homologue of the Drosophila gene, is located in 1q21.3, a region highly amplified in human sarcomas, malignant tumours of mesenchymal origin. Prune protein interacts with the metastasis suppressor nm23-H1, bu t shows impaired affinity towards the nm23-H1 S120G mutant associated with advanced neuroblastoma. Based on these observations, we previously suggeste d that prune may act as a negative regulator of nm23-H1 activity. We found amplification of PRUNE in aggressive sarcoma subtypes, such as leiomyosarco mas and malignant fibrous histiocytomas (NIFH) as well as in the less malig nant liposarcomas. PRUNE amplification was generally accompanied by high mR NA and moderate to high protein levels. The sarcoma samples expressed nm23- H1 mostly at low or moderate levels, whereas mRNA and protein levels were m oderate to high in breast carcinomas. For the more aggressive sarcoma subty pes, 9/13 patients with PRUNE amplification developed metastases. A similar situation was observed in all breast carcinomas with amplification of PRUN E. Infection of NIH3T3 cells with a PRUNE recombinant retrovirus increased cell proliferation. Possibly, amplification and overexpression of PRUNE has the same effect in the tumours. We suggest that amplification and overexpr ession of PRUNE could be a mechanism for inhibition of nm23-H1 activity tha t affect the development or progression of these tumours.