Correlation of human Bub1 expression with tumor-proliferating activity in salivary gland tumors.
Human Bub1 plays an important role at the spindle assembly check-point to prevent cell cycle progression following spindle damage. We examined the expression of Bub1 mRNA and protein in 21 human salivary gland tumors (7 pleomorphic adenomas, 2 warthin tumors, 5 mucoepidermoid carcinomas, 3 adenoid cystic carcinomas and 4 acinic cell carcinomas) and 3 normal submandibular glands using real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) or western blotting. The mean expression levels of Bub1 mRNA and protein were higher in malignant tumors (0.12+/-0.028/1.75+/-0.53) than normal submandibular glands (0.042+/-0.014/0.19+/-0.044) and benign tumors (0.058+/-0.01/0.97+/-0.44). We found a significant association between the level of Bub1 mRNA/protein expression and clinical stage in malignant tumors (Mann-Whitney U test, p=0.019/p=0.016). We analyzed its relation with the proliferative activity monitored by the Ki-67 labeling index by immunohistochemistry as well as the expression of proliferating cell nuclear antigen (PCNA) by Western blotting. A significant correlation was found between Bub1 mRNA/protein expression and the Ki-67 labeling index in salivary gland tumors (Spearman's correlation coefficient by rank test, p=0.026/p=0.002). These results indicate that increased expression of the human Bub1 gene is closely linked to abnormal cell proliferation in malignant conditions.
Shigeishi
Hideo
H
Division of Cervico-Gnathostomatology, Department of Oral and Maxillofacial Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
Yoneda
Shingo
S
Taki
Masayuki
M
Nobumori
Takeshi
T
Ohta
Kouji
K
Higashikawa
Koichiro
K
Yasui
Wataru
W
Kamata
Nobuyuki
N
D000235:Adenolymphoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008949:Adenoma, Pleomorphic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D018267:Carcinoma, Acinar Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018277:Carcinoma, Mucoepidermoid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D009367:Neoplasm Staging; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011494:Protein Kinases / Q000032:analysis / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012468:Salivary Gland Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D011494:Protein Kinases; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases