Chen Y K, Hsue S S, Lin L M
Oral Pathology Department, School of Dentistry, Kaohsiung Medical University, Kaohsiung, Taiwan.
Oral Dis. 2003 Sep;9(5):235-40. doi: 10.1034/j.1601-0825.2003.02920.x.
Abnormalities in the p53 gene are regarded as the most consistent genetic abnormalities detected in head and neck squamous cell carcinogenesis. Two new members of the p53 gene family, p73 at the 1p36 region and p63 at the 3q27-29 region, have recently been identified. They share considerable sequence homology with p53 in the transactivation, DNA binding, and oligomerization domains, indicating possible involvement in carcinogenesis. To our knowledge, however, p63 expression in experimental oral carcinogenesis has not been studied.
Immunohistochemical analysis of p63 protein expression was performed in 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch squamous cell carcinogenesis. Fifty outbred, young (6 weeks), male, Syrian golden hamsters (Mesocricatus auratus) were randomly divided into three experimental groups (each consisting of 10 3-, 9- and 15-week DMBA treated animals), 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.
In all of the untreated and mineral oil-treated pouch mucosa, nuclear positivity for p63 was mainly observed in the basal/parabasal cell layers. The p63 nuclear positivity extended from the basal/parabasal layers to the whole epithelial layers in the 3- and 9-week DMBA-treated pouch mucosa. Furthermore, the positive nuclear-stain cells were randomly distributed throughout the entire epithelial layers in the 3- and 9-week DMBA-treated pouch-mucosa specimens. In carcinomas from 15-week DMBA-treated pouch specimens, p63 staining was more uniform and homogeneous for the less-differentiated tumor areas. By contrast, p63 expression was noted mainly in the peripheral cells of tumor nests in the well-differentiated tumor areas.
The results of this study are consistent with those from previous analyses of p63 expression in human oral mucosa, suggesting that p63 may be associated with the regulation of epithelial differentiation and proliferation in DMBA-induced hamster buccal pouch squamous cell carcinogenesis. Further study is required to investigate which p63 isoform(s) is/are involved in hamster buccal pouch carcinogenesis.
p53基因异常被认为是在头颈部鳞状细胞癌发生过程中检测到的最一致的基因异常。最近，p53基因家族的两个新成员被鉴定出来，位于1p36区域的p73和位于3q27 - 29区域的p63。它们在反式激活、DNA结合和寡聚化结构域与p53有相当的序列同源性，表明可能参与致癌过程。然而，据我们所知，尚未研究p63在实验性口腔癌发生中的表达。
对7,12 - 二甲基苯并[a]蒽（DMBA）诱导的仓鼠颊囊鳞状细胞癌发生过程进行p63蛋白表达的免疫组织化学分析。50只杂种、年轻（6周）、雄性叙利亚金仓鼠（Mesocricatus auratus）被随机分为三个实验组（每组由10只分别接受3周、9周和15周DMBA处理的动物组成）和两个对照组（每组10只动物）。三个实验组的颊囊每周双侧涂抹三次0.5% DMBA溶液。其中一个对照组动物的处理方案相同，只是涂抹矿物油，而另一个对照组在整个实验过程中不做处理。
在所有未处理和矿物油处理的颊囊黏膜中，p63的核阳性主要见于基底/副基底细胞层。在接受3周和9周DMBA处理的颊囊黏膜中，p63核阳性从基底/副基底层扩展至整个上皮层。此外，在接受3周和9周DMBA处理的颊囊黏膜标本中，阳性核染色细胞随机分布于整个上皮层。在接受15周DMBA处理的颊囊标本的癌组织中，p63染色在低分化肿瘤区域更均匀一致。相比之下，在高分化肿瘤区域，p63表达主要见于肿瘤巢的周边细胞。
本研究结果与先前关于p63在人类口腔黏膜中表达的分析结果一致，提示p63可能与DMBA诱导的仓鼠颊囊鳞状细胞癌发生过程中的上皮分化和增殖调控有关。需要进一步研究以调查哪种p63亚型参与仓鼠颊囊癌发生。
