Modulation of Ki67, p53 and RARbeta expression in normal, premalignant and malignant human oral epithelial cells by chemopreventive agents.
BACKGROUND
Aberrant expression of Ki67, p53 and RARbeta are characteristic of many tumor types including those of the oral cavity. Chemopreventive agents may act by modulating their expression to more normal levels.


METHODS
The effects of 21 chemopreventive agents on the expression of Ki67, p53 and RARbeta were determined using a human in vitro model of normal, premalignant and malignant oral epithelial cell lines.


RESULTS
Ki67 and mutant p53 (mtp53) were overexpressed in both the premalignant and malignant cell lines, whereas expression of RARbeta was high in the normal, low in the premalignant and not detectable in the malignant cell lines. Most of the agents selectively inhibited the expression of Ki67 in the premalignant and malignant cell lines. Eight of the 21 agents increased, while four agents decreased, the levels of mtp53 protein in the premalignant cell line. In the malignant cell line, five of the agents increased, while ten agents decreased mtp53 protein levels. The agents increased RARbeta expression to near normal levels in the premalignant cell line.


CONCLUSIONS
The data suggest that the suppression of Ki67 and mtp53 are good indicators of the effectiveness of agents in premalignant and malignant oral cells, whereas the enhancement of RARbeta is a measure of effectiveness in premalignant oral cells.
D'Ambrosio
S M
SM
The Ohio State University School of Medicine and Public Health and Comprehensive Cancer Center, Columbus 43210, USA. dambrosio.1@osu.edu
Gibson-D'Ambrosio
R E
RE
Wani
G
G
Casto
B
B
Milo
G E
GE
Kelloff
G J
GJ
Steele
V E
VE
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D009061:Mouth Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000517:prevention & control; D011230:Precancerous Conditions / Q000378:metabolism / Q000517:prevention & control; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D012176:Retinoids / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D016588:Anticarcinogenic Agents; D019394:Ki-67 Antigen; D018168:Receptors, Retinoic Acid; D012176:Retinoids; D016159:Tumor Suppressor Protein p53; C082925:retinoic acid receptor beta