Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, India.
PLoS One. 2013 Jul 30;8(7):e70688. doi: 10.1371/journal.pone.0070688. Print 2013.
Keratins are structural marker proteins with tissue specific expression; however, recent reports indicate their involvement in cancer progression. Previous study from our lab revealed deregulation of many genes related to structural molecular integrity including KRT76. Here we evaluate the role of KRT76 downregulation in oral precancer and cancer development.
We evaluated KRT76 expression by qRT-PCR in normal and tumor tissues of the oral cavity. We also analyzed K76 expression by immunohistochemistry in normal, oral precancerous lesion (OPL), oral squamous cell carcinoma (OSCC) and in hamster model of oral carcinogenesis. Further, functional implication of KRT76 loss was confirmed using KRT76-knockout (KO) mice.
We observed a strong association of reduced K76 expression with increased risk of OPL and OSCC development. The buccal epithelium of DMBA treated hamsters showed a similar trend. Oral cavity of KRT76-KO mice showed preneoplastic changes in the gingivobuccal epithelium while no pathological changes were observed in KRT76 negative tissues such as tongue.
The present study demonstrates loss of KRT76 in oral carcinogenesis. The KRT76-KO mice data underlines the potential of KRT76 being an early event although this loss is not sufficient to drive the development of oral cancers. Thus, future studies to investigate the contributing role of KRT76 in light of other tumor driving events are warranted.
角蛋白是具有组织特异性表达的结构标记蛋白；然而，最近的报告表明它们参与了癌症的进展。我们实验室之前的一项研究表明，许多与结构分子完整性相关的基因失调，包括 KRT76。在这里，我们评估 KRT76 下调在口腔癌前病变和癌症发展中的作用。
我们通过 qRT-PCR 评估了口腔正常组织和肿瘤组织中 KRT76 的表达。我们还通过免疫组织化学分析了正常、口腔癌前病变（OPL）、口腔鳞状细胞癌（OSCC）和口腔致癌发生的仓鼠模型中的 K76 表达。此外，我们使用 KRT76 敲除（KO）小鼠证实了 KRT76 缺失的功能意义。
我们观察到 K76 表达减少与 OPL 和 OSCC 发展风险增加之间存在很强的相关性。DMBA 处理的仓鼠颊黏膜也显示出类似的趋势。KRT76-KO 小鼠的口腔显示出龈颊上皮的癌前变化，而在 KRT76 阴性组织（如舌）中没有观察到病理变化。
本研究表明 KRT76 在口腔癌发生中丢失。KRT76-KO 小鼠的数据强调了 KRT76 作为早期事件的潜力，尽管这种丢失不足以驱动口腔癌的发展。因此，有必要进行进一步的研究，以调查 KRT76 在其他肿瘤驱动事件中的作用。
