Concerted overexpression of the genes encoding p21 and cyclin D1 is associated with growth inhibition and differentiation in various carcinomas

• Published in: Molecular pathology Vol. 52; no. 2; pp. 78 - 83
• Main Authors: de Jong, J S, van Diest, P J, Michalides, R J, Baak, J P
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and Association of Clinical Pathologists 01.04.1999; BMJ
• Subjects: Biological and medical sciences; Blotting, Western; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Cell Differentiation - genetics; Cell Division - genetics; Cyclin D1 - genetics; Cyclin D1 - metabolism; Cyclin-Dependent Kinase Inhibitor p21; Cyclins - genetics; Cyclins - metabolism; Enzyme Inhibitors - metabolism; Female; Fluorescent Antibody Technique; General aspects; Humans; Immunoenzyme Techniques; Medical sciences; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - pathology; Tumor Cells, Cultured; Tumors; Up-Regulation; Adenocarcinoma; Human; Immunohistochemistry; Cell proliferation; Squamous cell carcinoma; Carcinoma; Double labelling; Gene overexpression; Malignant tumor; Cyclin D1; Cell differentiation; Gene expression; Carcinogenesis; Female genital diseases; Pathology; Mammary gland diseases; Ovarian diseases; Ovary; Head and neck; ENT disease; Mammary gland; Immunofluorescence
• ISSN: 1366-8714; 1472-4154
• DOI: 10.1136/mp.52.2.78

AIMS: To investigate the expression of the genes encoding cyclin D1 and p21 in proliferative and non-proliferative cells, as demonstrated by the Ki67 antibody, and to correlate these findings with differentiation. METHODS: Immunohistochemistry and immunofluorescence double staining were performed on three breast cancers, two squamous cell cancers of the head and neck, and one ovarium cystadenocarcinoma. In addition, the in vitro effect of cyclin D1 on p21 gene expression in MCF7 breast cancer cells was evaluated. RESULTS: Immunofluorescence double staining showed a differentiation related gradient in the detection of the Ki67 antigen, cyclin D1, and p21 in squamous cell cancers of the head and neck: Ki67 was detected in the basal layers of the tumour and the cyclin D1 and p21 genes were coexpressed in the higher, more differentiated layers of the tumour. The breast and ovarian cancers often had cells that coexpressed the p21 and cyclin D1 genes, whereas coexpression of cyclin D1 and Ki67 did not occur. Western blot analysis of the MCF7 breast cancer cells showed an upregulation of p21 production when cyclin D1 gene expression was induced. CONCLUSION: Overexpression of the cyclin D1 gene seems to lead to growth arrest in a variety of human cancers, possibly through the induction of p21 by cyclin D1. In squamous cell cancer, concerted overexpression of the genes encoding cyclin D1 and p21 might also induce differentiation.