Alteration of prb/p16/cdk4 regulation in human osteosarcoma

M. Serena Benassi, Lara Molendini, Gabriella Gamberi, Paola Ragazzini, M. Rosa Sollazzo, Mara Merli, Julia Asp, Giovanna Magagnoli

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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 languageEnglish
Pages (from-to)489-493
Number of pages5
JournalInternational Journal of Cancer
Volume84
Issue number5
Publication statusPublished - 1999

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Osteosarcoma
Methylation
Cyclins
Neoplasms
Neoplasm Metastasis
Cell Cycle
p16 Genes
CpG Islands
Cyclin-Dependent Kinases
Proteins
Phosphotransferases
Down-Regulation
Genes

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 journalArticle

Serena Benassi, M, Molendini, L, Gamberi, G, Ragazzini, P, Rosa Sollazzo, M, Merli, M, Asp, J & Magagnoli, G 1999, 'Alteration of prb/p16/cdk4 regulation in human osteosarcoma', International Journal of Cancer, vol. 84, no. 5, pp. 489-493.
Serena Benassi M, Molendini L, Gamberi G, Ragazzini P, Rosa Sollazzo M, Merli M et al. Alteration of prb/p16/cdk4 regulation in human osteosarcoma. International Journal of Cancer. 1999;84(5):489-493.
Serena Benassi, M. ; Molendini, Lara ; Gamberi, Gabriella ; Ragazzini, Paola ; Rosa Sollazzo, M. ; Merli, Mara ; Asp, Julia ; Magagnoli, Giovanna. / Alteration of prb/p16/cdk4 regulation in human osteosarcoma. In: International Journal of Cancer. 1999 ; Vol. 84, No. 5. pp. 489-493.
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