TY - JOUR
T1 - Amplification and overexpression of PRUNE in human sarcomas and breast carcinomas - a possible mechanism for altering the nm23-H1 activity
AU - Forus, Anne
AU - D'angelo, Anna
AU - Henriksen, Jørn
AU - Merla, Giuseppe
AU - Maelandsmo, Gunhild M.
AU - Flørenes, Vivi Ann
AU - Olivieri, Stefano
AU - Bjerkehagen, Bodil
AU - Meza-Zepeda, Leonardo A.
AU - Blanco, Francesca Del Vecchio
AU - Müller, Christoph
AU - Sanvito, Francesca
AU - Kononen, Juha
AU - Nesland, Jahn M.
AU - Fodstad, Øystein
AU - Reymond, Alexandre
AU - Kallioniemi, Olli P.
AU - Arrigoni, Gianluigi
AU - Ballabio, Andrea
AU - Myklebost, Ola
AU - Zollo, Massimo
PY - 2001/10/18
Y1 - 2001/10/18
N2 - 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, but shows impaired affinity towards the nm23-H1 S120G mutant associated with advanced neuroblastoma. Based on these observations, we previously suggested that prune may act as a negative regulator of nm23-H1 activity. We found amplification of PRUNE in aggressive sarcoma subtypes, such as leiomyosarcomas and malignant fibrous histiocytomas (MFH) as well as in the less malignant liposarcomas. PRUNE amplification was generally accompanied by high mRNA and moderate to high protein levels. The sarcoma samples expressed nm23-H1 mostly at low or moderate levels, whereas mRNA and protein levels were moderate to high in breast carcinomas. For the more aggressive sarcoma subtypes, 9/13 patients with PRUNE amplification developed metastases. A similar situation was observed in all breast carcinomas with amplification of PRUNE. 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 overexpression of PRUNE could be a mechanism for inhibition of nm23-H1 activity that affect the development or progression of these tumours.
AB - 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, but shows impaired affinity towards the nm23-H1 S120G mutant associated with advanced neuroblastoma. Based on these observations, we previously suggested that prune may act as a negative regulator of nm23-H1 activity. We found amplification of PRUNE in aggressive sarcoma subtypes, such as leiomyosarcomas and malignant fibrous histiocytomas (MFH) as well as in the less malignant liposarcomas. PRUNE amplification was generally accompanied by high mRNA and moderate to high protein levels. The sarcoma samples expressed nm23-H1 mostly at low or moderate levels, whereas mRNA and protein levels were moderate to high in breast carcinomas. For the more aggressive sarcoma subtypes, 9/13 patients with PRUNE amplification developed metastases. A similar situation was observed in all breast carcinomas with amplification of PRUNE. 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 overexpression of PRUNE could be a mechanism for inhibition of nm23-H1 activity that affect the development or progression of these tumours.
KW - Breast
KW - nm23
KW - PRUNE
KW - Sarcoma
UR - http://www.scopus.com/inward/record.url?scp=0035909509&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035909509&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1204874
DO - 10.1038/sj.onc.1204874
M3 - Article
C2 - 11687967
AN - SCOPUS:0035909509
VL - 20
SP - 6881
EP - 6890
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 47
ER -