MDM-2 is an
oncoprotein that seems to function, at least in part, by interacting with the p53
protein and modulating its
tumor-suppressing activity. The MDM-2 gene codes for p57, p74, p76, p85, and p90
proteins. Overexpression of only the p90
MDM-2 protein has been reported in
sarcomas showing MDM-2 gene amplification. In addition, post-transcriptional mechanisms have been demonstrated to play a role in the expression of MDM-2
proteins. We investigated MDM-2 gene amplification,
mRNA and
protein levels in various cases of
sarcomas. We found MDM-2 gene amplification in 12 (26%) of 46 cases of
sarcoma: 11 of 13 cases of
liposarcoma and 1 of 6 cases of
malignant fibrous histiocytoma. The MDM-2 amplification correlated with the presence of elevated levels of
mRNA and
protein in the
liposarcomas. In
sarcomas other than
liposarcomas,
mRNA was overexpressed in 7 (30%) of 23 cases, without MDM-2 amplification. In 15 (62.5%) of 24 cases of
sarcoma and in 1 case of
lipoma the
MDM-2 protein was overexpressed as shown by Western blot analysis. Interestingly, p57 not p90 was the most commonly overexpressed
MDM-2 protein. These data indicate that the molecular abnormalities affecting MDM-2 expression in cases of
sarcoma include transcriptional, post-transcriptional, and gene dosage (amplification) mechanisms. Furthermore, our findings suggest that MDM-2 p57
protein may be as important as p90 in the pathogenesis of human
sarcomas.