Altered G1 phase regulation in osteosarcoma

M. Serena Benassi, Lara Molendini, Gabriella Gamberi, M. Rosa Sollazzo, Paola Ragazzini, Mara Merli, Giovanna Magagnoli, Luca Sangiorgi, Patrizia Bacchini, Franco Bertoni, Piero Picci

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Alterations in the normal cell cycle lead to abnormal cell proliferation and to tumor development. To explore the role of the cyclin D/Cdk4 complex and the retinoblastoma protein (pRb) in the growth and spread of osteoblastic osteosarcoma (OS), 40 tumor samples were selected. In 17 of these cases, lung metastases occurred during follow-up. Expression of pRb, cyclin DI and its catalytic subunit, Cdk4, was studied by immunohistochemistry and immunoblotting. As controls, non-neoplastic tissues surrounding the tumor were used. The expression level and pattern were compared to clinical outcome. Cdk4 was over-expressed in 80% of OS, independently of clinical outcome, and showed an intense and uniform distribution in tumor cells compared to normal cells. However, co-immunoprecipitation of Cdk4 with cyclin DI revealed low levels of cyclin D/Cdk4 complex; 20 of 40 OS examined had a negative or minimal immunostaining for active pRb. The probability of relapse was significantly higher in pRb-negative than in the -positive patients (p <0.05). The ratio of unphosphorylated/hyperphosphorylated pRb was lower in relapsed patients than in patients with no evident disease, though the difference was not statistically significant. High levels of pRb/cyclin DI were found in all samples exhibiting functional pRb expression. Our results show that G1 phase deregulation is involved in formation and development of OS. The expression levels of both pRb and cyclin DI had a clear correlation with clinical outcome, suggesting that these parameters could be used as prognostic markers.

Original languageEnglish
Pages (from-to)518-522
Number of pages5
JournalInternational Journal of Cancer
Volume74
Issue number5
DOIs
Publication statusPublished - 1997

Fingerprint

Cyclins
G1 Phase
Osteosarcoma
Cyclin D
Neoplasms
Retinoblastoma Protein
Immunoprecipitation
Immunoblotting
Catalytic Domain
Cell Cycle
Immunohistochemistry
Cell Proliferation
Neoplasm Metastasis
Recurrence
Lung
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Altered G1 phase regulation in osteosarcoma. / Benassi, M. Serena; Molendini, Lara; Gamberi, Gabriella; Sollazzo, M. Rosa; Ragazzini, Paola; Merli, Mara; Magagnoli, Giovanna; Sangiorgi, Luca; Bacchini, Patrizia; Bertoni, Franco; Picci, Piero.

In: International Journal of Cancer, Vol. 74, No. 5, 1997, p. 518-522.

Research output: Contribution to journalArticle

Benassi, MS, Molendini, L, Gamberi, G, Sollazzo, MR, Ragazzini, P, Merli, M, Magagnoli, G, Sangiorgi, L, Bacchini, P, Bertoni, F & Picci, P 1997, 'Altered G1 phase regulation in osteosarcoma', International Journal of Cancer, vol. 74, no. 5, pp. 518-522. https://doi.org/10.1002/(SICI)1097-0215(19971021)74:5<518::AID-IJC7>3.0.CO;2-6
Benassi, M. Serena ; Molendini, Lara ; Gamberi, Gabriella ; Sollazzo, M. Rosa ; Ragazzini, Paola ; Merli, Mara ; Magagnoli, Giovanna ; Sangiorgi, Luca ; Bacchini, Patrizia ; Bertoni, Franco ; Picci, Piero. / Altered G1 phase regulation in osteosarcoma. In: International Journal of Cancer. 1997 ; Vol. 74, No. 5. pp. 518-522.
@article{fbccb2647b00432790e8c68978bbb176,
title = "Altered G1 phase regulation in osteosarcoma",
abstract = "Alterations in the normal cell cycle lead to abnormal cell proliferation and to tumor development. To explore the role of the cyclin D/Cdk4 complex and the retinoblastoma protein (pRb) in the growth and spread of osteoblastic osteosarcoma (OS), 40 tumor samples were selected. In 17 of these cases, lung metastases occurred during follow-up. Expression of pRb, cyclin DI and its catalytic subunit, Cdk4, was studied by immunohistochemistry and immunoblotting. As controls, non-neoplastic tissues surrounding the tumor were used. The expression level and pattern were compared to clinical outcome. Cdk4 was over-expressed in 80{\%} of OS, independently of clinical outcome, and showed an intense and uniform distribution in tumor cells compared to normal cells. However, co-immunoprecipitation of Cdk4 with cyclin DI revealed low levels of cyclin D/Cdk4 complex; 20 of 40 OS examined had a negative or minimal immunostaining for active pRb. The probability of relapse was significantly higher in pRb-negative than in the -positive patients (p <0.05). The ratio of unphosphorylated/hyperphosphorylated pRb was lower in relapsed patients than in patients with no evident disease, though the difference was not statistically significant. High levels of pRb/cyclin DI were found in all samples exhibiting functional pRb expression. Our results show that G1 phase deregulation is involved in formation and development of OS. The expression levels of both pRb and cyclin DI had a clear correlation with clinical outcome, suggesting that these parameters could be used as prognostic markers.",
author = "Benassi, {M. Serena} and Lara Molendini and Gabriella Gamberi and Sollazzo, {M. Rosa} and Paola Ragazzini and Mara Merli and Giovanna Magagnoli and Luca Sangiorgi and Patrizia Bacchini and Franco Bertoni and Piero Picci",
year = "1997",
doi = "10.1002/(SICI)1097-0215(19971021)74:5<518::AID-IJC7>3.0.CO;2-6",
language = "English",
volume = "74",
pages = "518--522",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "5",

}

TY - JOUR

T1 - Altered G1 phase regulation in osteosarcoma

AU - Benassi, M. Serena

AU - Molendini, Lara

AU - Gamberi, Gabriella

AU - Sollazzo, M. Rosa

AU - Ragazzini, Paola

AU - Merli, Mara

AU - Magagnoli, Giovanna

AU - Sangiorgi, Luca

AU - Bacchini, Patrizia

AU - Bertoni, Franco

AU - Picci, Piero

PY - 1997

Y1 - 1997

N2 - Alterations in the normal cell cycle lead to abnormal cell proliferation and to tumor development. To explore the role of the cyclin D/Cdk4 complex and the retinoblastoma protein (pRb) in the growth and spread of osteoblastic osteosarcoma (OS), 40 tumor samples were selected. In 17 of these cases, lung metastases occurred during follow-up. Expression of pRb, cyclin DI and its catalytic subunit, Cdk4, was studied by immunohistochemistry and immunoblotting. As controls, non-neoplastic tissues surrounding the tumor were used. The expression level and pattern were compared to clinical outcome. Cdk4 was over-expressed in 80% of OS, independently of clinical outcome, and showed an intense and uniform distribution in tumor cells compared to normal cells. However, co-immunoprecipitation of Cdk4 with cyclin DI revealed low levels of cyclin D/Cdk4 complex; 20 of 40 OS examined had a negative or minimal immunostaining for active pRb. The probability of relapse was significantly higher in pRb-negative than in the -positive patients (p <0.05). The ratio of unphosphorylated/hyperphosphorylated pRb was lower in relapsed patients than in patients with no evident disease, though the difference was not statistically significant. High levels of pRb/cyclin DI were found in all samples exhibiting functional pRb expression. Our results show that G1 phase deregulation is involved in formation and development of OS. The expression levels of both pRb and cyclin DI had a clear correlation with clinical outcome, suggesting that these parameters could be used as prognostic markers.

AB - Alterations in the normal cell cycle lead to abnormal cell proliferation and to tumor development. To explore the role of the cyclin D/Cdk4 complex and the retinoblastoma protein (pRb) in the growth and spread of osteoblastic osteosarcoma (OS), 40 tumor samples were selected. In 17 of these cases, lung metastases occurred during follow-up. Expression of pRb, cyclin DI and its catalytic subunit, Cdk4, was studied by immunohistochemistry and immunoblotting. As controls, non-neoplastic tissues surrounding the tumor were used. The expression level and pattern were compared to clinical outcome. Cdk4 was over-expressed in 80% of OS, independently of clinical outcome, and showed an intense and uniform distribution in tumor cells compared to normal cells. However, co-immunoprecipitation of Cdk4 with cyclin DI revealed low levels of cyclin D/Cdk4 complex; 20 of 40 OS examined had a negative or minimal immunostaining for active pRb. The probability of relapse was significantly higher in pRb-negative than in the -positive patients (p <0.05). The ratio of unphosphorylated/hyperphosphorylated pRb was lower in relapsed patients than in patients with no evident disease, though the difference was not statistically significant. High levels of pRb/cyclin DI were found in all samples exhibiting functional pRb expression. Our results show that G1 phase deregulation is involved in formation and development of OS. The expression levels of both pRb and cyclin DI had a clear correlation with clinical outcome, suggesting that these parameters could be used as prognostic markers.

UR - http://www.scopus.com/inward/record.url?scp=0030611932&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030611932&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1097-0215(19971021)74:5<518::AID-IJC7>3.0.CO;2-6

DO - 10.1002/(SICI)1097-0215(19971021)74:5<518::AID-IJC7>3.0.CO;2-6

M3 - Article

C2 - 9355974

AN - SCOPUS:0030611932

VL - 74

SP - 518

EP - 522

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 5

ER -