Singh Abhishek, Jain Anshi, Shetty Devi Charan, Rathore Ajit Singh, Juneja Saurabh
Department of Oral Pathology and Microbiology, ITS Dental College, Muradnagar, Ghaziabad, Uttar Pradesh, India.
J Cancer Res Ther. 2020 Apr-Jun;16(3):521-529. doi: 10.4103/jcrt.JCRT_659_18.
Oncogenes and tumor suppressor genes play a major role in cancer formation, growth, and progression. One of the important findings in this area is that murine double minute 2 (MDM2) oncogene is a negative regulator of wild-type p53. In tumors, expressing wild-type p53, inhibition of MDM2 expression will stabilize p53 and allow it to perform its proapoptotic function, while simultaneously preventing MDM2 from exerting its p53-independent oncogenic effects. The intracellular levels of p53 are tightly regulated by MDM2, as it is a key player in autoregulatory feedback loop under nonstressed conditions. The p53-MDM2 relationship is vital not only for essential functions of the cell, but it also appears to be an integrated part of the complex cellular network which supports the importance of this affair and is a hallmark for its coexistence.
This study was designed to identify immunohistochemically the expression of p53 and MDM2 gene using monoclonal antibody in 60 cases of formalin-fixed paraffin-embedded tissue blocks, of which 20 cases were of solid multicystic ameloblastoma (SMA), 20 cases were of odontogenic keratocyst (OKC), and 20 cases were of unicystic ameloblastoma (UA).
Immunoexpression of p53 and MDM2 was highest in OKC followed by SMA and was minimum in UA. Further results showed positive correlation between both the molecules.
The studied showed that the relationship has a significant role in cancer etiology and progression and therefore is an important topic for future research which should help in the development of new therapeutic agent against cancer.
癌基因和肿瘤抑制基因在癌症的形成、生长和进展中起主要作用。该领域的一项重要发现是,小鼠双微体2(MDM2)癌基因是野生型p53的负调节因子。在表达野生型p53的肿瘤中,抑制MDM2表达将使p53稳定,并使其发挥促凋亡功能,同时防止MDM2发挥其不依赖p53的致癌作用。p53的细胞内水平受到MDM2的严格调控,因为它是在非应激条件下自动调节反馈回路中的关键参与者。p53-MDM2关系不仅对细胞的基本功能至关重要,而且似乎是复杂细胞网络的一个组成部分,这支持了此事的重要性,并且是其共存的一个标志。
本研究旨在使用单克隆抗体通过免疫组织化学方法鉴定60例福尔马林固定石蜡包埋组织块中p53和MDM2基因的表达,其中20例为实性多囊性成釉细胞瘤(SMA),20例为牙源性角化囊肿(OKC),20例为单囊性成釉细胞瘤(UA)。
p53和MDM2的免疫表达在OKC中最高,其次是SMA,在UA中最低。进一步结果显示这两种分子之间呈正相关。
研究表明,这种关系在癌症病因学和进展中具有重要作用,因此是未来研究的一个重要课题,这应该有助于开发新的抗癌治疗药物。