Analysis of cyclin D1 and CDK expression in colonic polyps containing neoplastic foci: a study of proteins extracted from paraffin sections.
Overexpression or amplification of G1 cyclins has been demonstrated in various types of human cancers. Overexpression of cyclin D1, an accelerator of cell cycle, is thought to be an early event in colonic multistage carcinogenesis, but its expression at transformation from benign to neoplastic foci is not clear. We analyzed the expression of cyclin D1 and its catalystic partner CDK4 in colon polyps containing neoplastic foci. For direct comparison of the expression in adenomatous tissues and neoplastic foci, proteins in adequate amounts were extracted from paraffin embedded sections. Western blot and densitometry analyses showed that cyclin D1 expression was 2.3-times and 2.5-times higher in adenomatous tissues and neoplastic foci, compared with normal colonic mucosa. In contrast, the levels of CDK4 and CDK2 expression were only modestly increased in adenomatous tissues but significantly higher in neoplastic foci, relative to normal mucosa. Expression of PCNA, a cell proliferation marker, increased from normal mucosa to adenoma to focal cancer. Our findings suggest that overexpression of cyclin D1 may be associated with high proliferative activity in adenomatous tissues and that concurrent high expression of cyclin D1 and CDK4 may further perturb cell cycle progression and play a pivotal role in colonic carcinogenesis.
Izawa
Hikaru
H
Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, Osaka, Japan.
Yamamoto
Hirofumi
H
Ikeda
Masataka
M
Ikeda
Kimimasa
K
Fukunaga
Hiroki
H
Yasui
Masayoshi
M
Ikenaga
Masakazu
M
Sekimoto
Mitsugu
M
Monden
Takushi
T
Matsuura
Nariaki
N
Monden
Morito
M
D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D042846:CDC2-CDC28 Kinases; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D003111:Colonic Polyps / Q000378:metabolism* / Q000473:pathology; D019938:Cyclin D1 / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000378:metabolism; D016612:Paraffin Embedding; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; D019938:Cyclin D1; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495900:CDK4 protein, human; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases