Expression and significance of cell cycle-related proteins Cyclin Dl, CDK4, p27, E2F-l and Ets-1 in chondrosarcoma of the jaws

doi:10.1016/S1368-8375(00)00091-9

Oral Oncology

Volume 37, Issue 5, July 2001, Pages 431-436

https://doi.org/10.1016/S1368-8375(00)00091-9 Get rights and content

Abstract

To elucidate the expression and significance of cell cycle-associated proteins in chondrosarcoma of the jaws, Cyclin Dl, CDK4, p27, E2F-l and Ets-l expressions were examined in chondrosarcoma and osteochondroma of the jaws by immunohistochemical ABC method. The results demonstrated that Cyclin Dl, CDK4, p27, E2F-1 and Ets-1 were positive 75% (15 of 20), 60% (12 of 20), 25% (5 of 20), 65% (13 of 20) and 60% (12 of 20) in chondrosarcoma of the jaws, respectively. There was no remarkable difference in the expression of these proteins among histological grades of the chondrosarcoma (P>0.05). In osteochondroma of the jaws, CDK4 and E2F with an equal positivity of 12.5% (1 of 8), whereas p27 was positive 75% (6 of 8). None of the osteochondroma cases was immunohistochemically positive for Cycin Dl and Ets-1. In addition, the positive rate of Cyclin Dl, CDK4, E2F-l and Ets-1 proteins was significantly higher, whereas p27 was lower in chondrosarcoma than in osteochondroma of the jaws (P<0.05). These data show that the expression of cell cycle regulatory proteins is altered in chondrosarcoma of the jaws: cyclin Dl, CDK4, E2F-1 and Ets-1 are over-expressed and p27 is low-expressed.

Introduction

Cancer cells differ from normal cells in many respects and their growth ability correlates well with their tumorigenicity. The investigation of tumor cell proliferative activity provides insights into tumor biology. Proliferative activity has been correlated with progression and prognosis in a variety of malignant tumors. Recent advances in cell biology have elucidated precise mechanisms of cell cycle regulatory systems and have shown that deregulated cellular proliferation is a common feature in many cancers [1], [2], [3]. Cell cycle progression is regulated not only by various cyclins and cyclin-dependent kinase (CDK) complex and by many CDK-inhibitors such as p27, but also by other cell cycle-associated proteins such as nuclear transcriptional factor E2F-l and Ets-l [2], [3], [4], [5], [6]. To make clear these proteins alterations is helpful in understanding the occurrence and development of tumors. Immunohistochemical assessment of cell proliferation has advantages over the other techniques such as flow cytometric and mitotic frequency analysis, because the tissue architecture is intact and proliferating cells can be visualized in relation to other histological characteristics.

Chondrosarcoma is the second most frequent primary malignant tumor of bone. A better understanding of the development of chondrosarcoma of the jaws is important for the establishment of new treatment strategies. Only a few investigations have described chondrosarcoma at the molecular or cellular proliferation levels. The aim of this study was to detect the different patterns of expression of several cell cycle-associated proteins, including Cyclin Dl, CDK4, p27, E2F-l and Ets-l, in chondrosarcorma of the jaws by immunohistochemistry and to elucidate their roles in its development.

Section snippets

Tissue preparation

Twenty biopsies of patients with chondrosarcoma of the jaws were collected from the files of the Department of Oral Pathology, Fourth Military Medical University, during the period 1991–1998. The clinical data was reviewed to record age and sex of patients and site of lesions. The age range was 11–54 years (average 36 years). The sex ratio was 1 (F, 9 cases): 1.2 (M, 11 cases). Tissue samples were obtained surgically from 11 upper jaws and 9 lower jaws. None of the patients had received any

Results

The positive cells of Cycin Dl, CDK4, p27, E2F-1 and Ets-1 were distributed focally or diffusely. Both of Cyclin Dl and CDK4 positive responses were located in the cytoplasm and/or the nuclei, mainly in the nuclei (Fig. 1a, b). p27 positive stain was observed dominantly in the nuclei (Fig. 1c). E2F-l and Ets-1 was exclusively expressed in the nuclei (Fig. 1d, e). The positive rate of Cycin Dl, CDK4, p27, E2F-l and Ets-1 in chonchosarcoma was 75% (15 of 20), 60% (12 of 20), 25% (5 of 20), 65%

Discussion

The development of a tumor is a complicated multistage process which involves various genetic aberrations. The growth of cancer cells is characterized by accelerated passage through the cell cycle, which is often caused by deregulation of the G1-S transition. At the G1-S transition of the cell cycle, it is decided whether cells continue to progress through the cell cycle or become quiescent [5], [6]. This decision is controlled in part by extracellular factors stimulating or inhibiting growth

Acknowledgements

We thank Professor Yan Jin, Department of Oral Pathology, Stomatological College, Fourth Military Medical University, for his kind help in this study. We also thank Dr. Lianjun Yang, Department of Pathology, Fourth Military Medical University, for providing some useful references.

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Expression and significance of cell cycle-related proteins Cyclin Dl, CDK4, p27, E2F-l and Ets-1 in chondrosarcoma of the jaws

Abstract

Introduction

Section snippets

Tissue preparation

Results

Discussion

Acknowledgements

Ann Oncology

Oral Oncol

Oral Oncol

Lung Cancer

Curr Opin Genet Dev

Biochim Biophys Acta

Cyclins, cyclin-dependent kinases and cdk inhibitorsimplications in cell cycle control and cancer

Crit Rev Euk Gene Expr

Oncogenes and growth control

Biochim Biophys Acta

Identification of target genes of oncogenic transcription factors

Proc Soci Exp Biol Med.

Principles of CDK regulation

Nature

Nuclear cyclin Dl overexpression is a critical event associated with cell proliferation and invasive growth in gallbladder carcinogenesis

J Gastroenterol

The prognostic significance of p53, p21 (Waf1/Cip1), and cyclin Dl protein expression in esophageal cancer patients

Anticancer Res.

Conditional transformation of rat embryo flbroblast cells by a cyclin Dl-cdk4 fusion gene

Oncogene

Expression of cyclins and cdks throughout murine carcinogenesis

Cell Mol Biol.

Coamplification of the CDK4 gene with MDM2 and GLI in human sarcoma

Cancer Res.