Department of Hepatobiliary Surgery , The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Hepatol Res. 2009 Feb;39(2):177-86. doi: 10.1111/j.1872-034X.2008.00449.x.
To investigate the status of Phosphatidylinositol 3-kinase (PI3K)/PTEN/AKT/mammalian target of rapamycin (mTOR) pathway and its correlation with clinicopathological features and matrix metalloproteinase-2, -9 (MMP-2, 9) in human hepatocellular carcinoma (HCC).
PTEN, Phosphorylated AKT (p-AKT), Phosphorylated mTOR (p-mTOR), MMP-2, MMP-9 and Ki-67 expression levels were evaluated by immunohistochemistry on tissue microarrays containing 200 HCCs with paired adjacent non-cancerous liver tissues. PTEN, MMP-2 and MMP-9 mRNA levels were determined by real-time RT-PCR in 36 HCCs. The relationships between PI3K/PTEN/AKT/mTOR pathway and clinicopathological factors and MMP-2, 9 were analyzed in HCC.
In HCC, PTEN loss and overexpression of p-AKT and p-mTOR were associated with tumor grade, intrahepatic metastasis, vascular invasion, TNM stage and high Ki-67 labeling index (P < 0.05). PTEN loss was correlated with p-AKT, p-mTOR and MMP-9 overexpression. Furthermore, PTEN and MMP-2, 9 mRNA levels were down-regulated and up-regulated in HCC compared with paired non-cancerous liver tissues, respectively (P < 0.01). PTEN, MMP-2 and MMP-9 mRNA levels were correlated with tumor stage and metastasis. There was an inverse correlation between PTEN and MMP-9 mRNA expression. However, PI3K/PTEN/AKT/mTOR pathway was not correlated with MMP-2.
PI3K/PTEN/AKT/mTOR pathway, which is activated in HCC, is involved in invasion and metastasis through up-regulating MMP-9 in HCC.
研究磷脂酰肌醇 3-激酶（PI3K）/PTEN/AKT/哺乳动物雷帕霉素靶蛋白（mTOR）通路在人肝细胞癌（HCC）中的状态及其与临床病理特征的关系，并探讨其与基质金属蛋白酶-2（MMP-2）、-9（MMP-9）的相关性。
采用组织微阵列免疫组化法检测 200 例 HCC 及其配对癌旁非肿瘤组织中 PTEN、磷酸化 AKT（p-AKT）、磷酸化 mTOR（p-mTOR）、MMP-2、MMP-9 和 Ki-67 的表达水平，实时 RT-PCR 法检测 36 例 HCC 中 PTEN、MMP-2 和 MMP-9 的 mRNA 水平。分析 HCC 中 PI3K/PTEN/AKT/mTOR 通路与临床病理因素及 MMP-2、9 的关系。
在 HCC 中，PTEN 缺失和 p-AKT、p-mTOR 的过度表达与肿瘤分级、肝内转移、血管侵犯、TNM 分期和高 Ki-67 标记指数有关（P<0.05）。PTEN 缺失与 p-AKT、p-mTOR 和 MMP-9 的过度表达相关。此外，与配对癌旁非肿瘤组织相比，HCC 中 PTEN 和 MMP-2、9 的 mRNA 水平分别下调和上调（P<0.01）。PTEN、MMP-2 和 MMP-9 的 mRNA 水平与肿瘤分期和转移相关。PTEN 和 MMP-9 mRNA 表达呈负相关，而 PI3K/PTEN/AKT/mTOR 通路与 MMP-2 无关。
在 HCC 中激活的 PI3K/PTEN/AKT/mTOR 通路通过上调 HCC 中的 MMP-9 参与侵袭和转移。
