Abstract
Cell-cycle regulation depends on a fine balance between cyclin-cyclin-dependent kinase complexes and a family of kinase inhibitors that bind cyclin-cdk complexes and block their activity. To investigate the role of mechanisms regulating cell-cycle progression in human osteosarcomas (OS), pRb/p16/cdk4 expression was analyzed in 39 high-grade OS; 19 of these developed metastasis during follow-up. Positive reaction for functional pRB was shown by 18/39 (46%) OS, while 21/39 (54%) were negative. A higher probability of metastasis was seen in patients with negative pRb expression (p <0.05). Furthermore, while functional pRb and DI expression are inversely associated to metastasis occurrence, the presence of DI /cdk4 complex in our study was related to poor prognosis. We found that 10/18 pRb-positiye and 14/21 pRb-negative tumors were p 16-positive. No significant correlation was found between pRb and pi6 expression. On the other hand, high cdk4 levels in pie-positive tumors as compared with pie-negative tumors resulted in a positive association between pi6 and cdk4 expression (Chi squared = 5.98; p = 0.01). No extensive p16INK4A genomic alterations were found in tumors lacking pie-protein expression. To determine which mechanisms are involved in the down-regulation of p16 protein, the methylation status of the p16INK4 gene was evaluated on the 15 pie-negative tumors: 8 samples showed 5′ CpG-island methylation; 4/8 had a complete methylation status, while in the remaining 4 the gene was only partially methylated. These data confirm the role of the pRb/p16/cdk4 pathway in OS development.
| Original language | English |
|---|---|
| Pages (from-to) | 489-493 |
| Number of pages | 5 |
| Journal | International Journal of Cancer |
| Volume | 84 |
| Issue number | 5 |
| Publication status | Published - 1999 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Alteration of prb/p16/cdk4 regulation in human osteosarcoma. / Serena Benassi, M.; Molendini, Lara; Gamberi, Gabriella; Ragazzini, Paola; Rosa Sollazzo, M.; Merli, Mara; Asp, Julia; Magagnoli, Giovanna.
In: International Journal of Cancer, Vol. 84, No. 5, 1999, p. 489-493.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Alteration of prb/p16/cdk4 regulation in human osteosarcoma
AU - Serena Benassi, M.
AU - Molendini, Lara
AU - Gamberi, Gabriella
AU - Ragazzini, Paola
AU - Rosa Sollazzo, M.
AU - Merli, Mara
AU - Asp, Julia
AU - Magagnoli, Giovanna
PY - 1999
Y1 - 1999
N2 - Cell-cycle regulation depends on a fine balance between cyclin-cyclin-dependent kinase complexes and a family of kinase inhibitors that bind cyclin-cdk complexes and block their activity. To investigate the role of mechanisms regulating cell-cycle progression in human osteosarcomas (OS), pRb/p16/cdk4 expression was analyzed in 39 high-grade OS; 19 of these developed metastasis during follow-up. Positive reaction for functional pRB was shown by 18/39 (46%) OS, while 21/39 (54%) were negative. A higher probability of metastasis was seen in patients with negative pRb expression (p <0.05). Furthermore, while functional pRb and DI expression are inversely associated to metastasis occurrence, the presence of DI /cdk4 complex in our study was related to poor prognosis. We found that 10/18 pRb-positiye and 14/21 pRb-negative tumors were p 16-positive. No significant correlation was found between pRb and pi6 expression. On the other hand, high cdk4 levels in pie-positive tumors as compared with pie-negative tumors resulted in a positive association between pi6 and cdk4 expression (Chi squared = 5.98; p = 0.01). No extensive p16INK4A genomic alterations were found in tumors lacking pie-protein expression. To determine which mechanisms are involved in the down-regulation of p16 protein, the methylation status of the p16INK4 gene was evaluated on the 15 pie-negative tumors: 8 samples showed 5′ CpG-island methylation; 4/8 had a complete methylation status, while in the remaining 4 the gene was only partially methylated. These data confirm the role of the pRb/p16/cdk4 pathway in OS development.
AB - Cell-cycle regulation depends on a fine balance between cyclin-cyclin-dependent kinase complexes and a family of kinase inhibitors that bind cyclin-cdk complexes and block their activity. To investigate the role of mechanisms regulating cell-cycle progression in human osteosarcomas (OS), pRb/p16/cdk4 expression was analyzed in 39 high-grade OS; 19 of these developed metastasis during follow-up. Positive reaction for functional pRB was shown by 18/39 (46%) OS, while 21/39 (54%) were negative. A higher probability of metastasis was seen in patients with negative pRb expression (p <0.05). Furthermore, while functional pRb and DI expression are inversely associated to metastasis occurrence, the presence of DI /cdk4 complex in our study was related to poor prognosis. We found that 10/18 pRb-positiye and 14/21 pRb-negative tumors were p 16-positive. No significant correlation was found between pRb and pi6 expression. On the other hand, high cdk4 levels in pie-positive tumors as compared with pie-negative tumors resulted in a positive association between pi6 and cdk4 expression (Chi squared = 5.98; p = 0.01). No extensive p16INK4A genomic alterations were found in tumors lacking pie-protein expression. To determine which mechanisms are involved in the down-regulation of p16 protein, the methylation status of the p16INK4 gene was evaluated on the 15 pie-negative tumors: 8 samples showed 5′ CpG-island methylation; 4/8 had a complete methylation status, while in the remaining 4 the gene was only partially methylated. These data confirm the role of the pRb/p16/cdk4 pathway in OS development.
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M3 - Article
VL - 84
SP - 489
EP - 493
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 5
ER -