Diabetes enhances cell proliferation but not Bax/Bcl-2-mediated apoptosis during oral oncogenesis.
Markers of cell proliferation (Ki-67 antigen) and apoptosis (Bax, Bcl-2) were studied in an experimental model of chemically induced carcinogenesis in normal and diabetic (type I) Sprague-Dawley rats. Thirteen diabetic and 12 normal rats developed cancer after 4-nitroquinoline-N-oxide treatment, while 6 diabetic and 6 normal animals were used as controls. The biopsies were classified pathologically (from oral mucosal dysplasia to moderately differentiated squamous cell carcinoma) and studied immunohistochemically using monoclonal antibodies against Bax, Bcl-2 and Ki-67 proteins. The Bcl-2/Bax ratio was almost stable during the oncogenesis process in the diabetic rats, whereas the normal rats showed an increased Bcl-2/Bax ratio during the stage of moderately differentiated carcinoma. In contrast, Ki-67 expression was higher in diabetic rats than in normal ones in almost all stages of oral oncogenesis, and it reached significantly increased levels in the stages of normal control tissue, dysplasia and moderately differentiated squamous cell carcinoma. These data suggest that diabetes results in increased cell proliferation during oral oncogenesis, but this is accomplished without affecting the Bax/Bcl-2-mediated apoptotic pathways.
Vairaktaris
E
E
Department of Oral and Maxillofacial Surgery, University of Athens Medical School, Vas. Sofias 93 & Dim. Soutsou 1, Athens 11521, Greece. lvairakt@med.uoa.gr
Kalokerinos
G
G
Goutzanis
L
L
Yapijakis
C
C
Derka
S
S
Vassiliou
S
S
Spyridonidou
S
S
Vylliotis
A
A
Nkenke
E
E
Lazaris
A
A
Patsouris
E
E
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000378:metabolism*; D049109:Cell Proliferation; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D005260:Female; D019394:Ki-67 Antigen / Q000032:analysis; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein / Q000032:analysis*