Genome Biology Lab, Department of Biosciences, Jamia Millia Islamia, Maulana Mohammad Ali Jauhar Marg, New Delhi, 110025, India.
J Cancer Res Clin Oncol. 2012 Jan;138(1):103-9. doi: 10.1007/s00432-011-1077-y. Epub 2011 Oct 28.
The tumor suppressor gene PTEN negatively regulates Akt, a downstream mediator phosphoinositol 3-kinase. Several studies have reported the role of PTEN gene in Akt downregulation and apoptosis induction in different cancers and cell lines. However, the role of loss of PTEN expression in Akt activation and spontaneous apoptosis in oral squamous cell carcinoma clinical specimens is not well established.
We investigated the expression of PTEN and phospho-Akt in 146 formalin-fixed (archived) paraffin-embedded oral squamous cell carcinoma tissue sections through immunohistochemical analysis. Programmed cell death (apoptosis) was determined by Terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling assay.
Sixty-one percent loss of PTEN expression and 68.5% Akt activation was observed in oral squamous cell carcinoma. A significant correlation was found between loss of PTEN expression and Akt activation. Loss of PTEN expression and Akt activation were further correlated with different clinical parameters and found to be significantly correlated with tumor stage. Apoptotic index was estimated and correlated with PTEN expression and Akt activation. The percentage of apoptotic cells varied from 0.2 to 14.1%. Low apoptotic index was observed in 105 (72%) of samples, and it was found to be significantly related with loss of PTEN expression and phospho-Akt
The present study confirms the contribution of loss of PTEN expression in Akt phosphorylation and spontaneous apoptosis suppression in the specimens of oral cancer. Both PTEN and phospho-Akt are likely to be concerned with oral cancer progression and reduced incidence of spontaneous apoptosis.
抑癌基因 PTEN 负向调节 Akt，后者是磷酸肌醇 3-激酶的下游介质。几项研究报告称，PTEN 基因在不同癌症和细胞系中下调 Akt 和诱导细胞凋亡中发挥作用。然而，PTEN 表达缺失在口腔鳞状细胞癌临床标本中激活 Akt 和自发凋亡中的作用尚未得到充分证实。
我们通过免疫组织化学分析研究了 146 例福尔马林固定（存档）石蜡包埋口腔鳞状细胞癌组织切片中 PTEN 和磷酸化 Akt 的表达。通过末端脱氧核苷酸转移酶生物素-dUTP 缺口末端标记法测定程序性细胞死亡（凋亡）。
在口腔鳞状细胞癌中观察到 61%的 PTEN 表达缺失和 68.5%的 Akt 激活。PTEN 表达缺失与 Akt 激活之间存在显著相关性。PTEN 表达缺失和 Akt 激活与不同的临床参数进一步相关，并与肿瘤分期显著相关。估计凋亡指数并与 PTEN 表达和 Akt 激活相关。凋亡细胞的百分比从 0.2%到 14.1%不等。105 例（72%）样本中观察到低凋亡指数，与 PTEN 表达缺失和磷酸化 Akt 显著相关。
本研究证实了在口腔癌标本中，PTEN 缺失表达对 Akt 磷酸化和自发凋亡抑制的作用。PTEN 和磷酸化 Akt 都可能与口腔癌的进展和自发凋亡减少有关。
