title: Expression of survivin and XIAP for DMBA-induced hamster buccal pouch squamous cell carcinogenesis is associated with p53 accumulation.
abstract: Apoptosis (programmed cell death) is regulated by a number of inhibitory or stimulatory factors. One such family of antiapoptotic proteins is the inhibitors of apoptosis proteins (IAPs), of which survivin and X chromosome-linked IAP (XIAP) are members. The expression of survivin and XIAP, as well as their association with p53, in chemically-induced experimental oral carcinogenesis is not completely understood. The objective of the present study was, therefore, to investigate the protein expression of these two IAP family members and their relationship with p53 status, in 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch squamous cell carcinogenesis. Immunohistochemical analysis of survivin, XIAP and p53 protein expression was performed in DMBA-induced pouch squamous cell carcinogenesis. Fifty outbred, young (6 weeks), male Syrian golden hamsters (Mesocricatus auratus) were randomly divided into three experimental groups (each group consisting of 10 animals treated with DMBA for 3-, 7- or 14-weeks), and two control groups (with 10 animals in each). The pouches of the three experimental groups were painted bilaterally with a 0.5% DMBA solution three times a week. The treatment protocol for animals in one of the control groups was identical with only mineral oil applied, while the other control group remained untreated throughout the experiment. Survivin staining could not be detected by immunohistochemistry in any of the untreated or mineral oil treated hamster pouch-tissue specimens. Cytoplasmic staining of survivin proteins was apparent in the entire epithelial layer (excluding the keratinized layer) in all 3-week DMBA treated pouch-tissue analyzed. In addition, cytoplasmic survivin staining was observed in all specimens of 7- and 14-week DMBA treated pouch-tissue. XIAP positivity was confined to the outermost keratinized layer of the pouch-tissue from control animals and those treated with DMBA for 3-weeks. However, XIAP staining was detected in the whole epithelial layer (except the basal layer) in 7- and 14-week DMBA treated pouch-tissue. p53 was not detected in any untreated and mineral oil treated pouch-tissue, whereas nuclear p53 staining was observed for all 3-, 7- and 14-week DMBA treated pouch-tissue. The results of this study demonstrate the association between survivin/XIAP and p53 expression in this experimental model system for oral carcinogenesis, although their exact interactions remain to be clarified. Moreover, our findings suggest that the DMBA-induced hamster buccal pouch mucosa may serve as an appropriate experimental model for investigation of potential novel therapeutic tools for oral squamous-cell carcinomas.
authors.affiliation: Oral Pathology Department, School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Shue-Sang
authors.initials: SS
authors.lastname: Hsue
authors.forename: Yuk-Kwan
authors.initials: YK
authors.lastname: Chen
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Lin
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000378:metabolism*; D002610:Cheek; D006224:Cricetinae; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008647:Mesocricetus; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism*
chemical_list: C107489:BIRC5 protein, human; D002273:Carcinogens; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D015127:9,10-Dimethyl-1,2-benzanthracene