Expression of p27 is associated with Bax expression and spontaneous apoptosis in oral and oropharyngeal carcinoma.
p27Kip1, a cyclin-dependent kinase inhibitor, is a negative regulator of the cell cycle, and apoptosis is a genetically encoded program of cell death. To clarify the relationship between the cell cycle and apoptosis, we investigated expression of p27, cyclin D1 and apoptosis-related proteins (p53, Bax, Bcl-2 and c-Myc) in 60 cases of oral and oropharyngeal squamous-cell carcinoma (SCC) using an immuno-histochemical approach, and evaluated spontaneous apoptosis in vivo. Our most notable finding was that spontaneous apoptosis in the p27-positive group was significantly higher than that in the p27-negative group (p = 0.028). In addition, the percentage of p27-positive cells was clearly correlated with that of Bax-positive cells (gamma = 0.288, p = 0.028) and with that of cyclin D1-positive cells (gamma = 0.416, p = 0.002). Expression of p27 was inversely associated with the clinical stage of total tumor progression (p = 0.027). However, no correlation was found between p27 expression and the following parameters: gender, tumor size, lymph node metastasis, overall survival and disease-free survival. Our results give evidence that the action of the cell-cycle regulator p27 is closely linked with apoptosis in clinical samples from patients and indicate that over-expression of p27 might induce apoptosis in cancer cells through elevation of Bax expression, thereby acting on tumor progression.
Fujieda
S
S
Department of Otorhinolaryngology, Fukui Medical University, Yoshida, Japan. sfujieda@fmsrsa.fukui-med.ac.jp
Inuzuka
M
M
Tanaka
N
N
Sunaga
H
H
Fan
G K
GK
Ito
T
T
Sugimoto
C
C
Tsuzuki
H
H
Saito
H
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D018797:Cell Cycle Proteins; D019938:Cyclin D1 / Q000032:analysis; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005260:Female; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D009959:Oropharyngeal Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D019253:Proto-Oncogene Proteins c-bcl-2; D015996:Survival Rate; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27