McMenamin M E, Soung P, Perera S, Kaplan I, Loda M, Sellers W R
Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA.
Cancer Res. 1999 Sep 1;59(17):4291-6.
The tumor suppressor gene PTEN/MMAC-1/TEP-1 (referred to hereafter as PTEN) maps to chromosome 10q23 and encodes a dual specificity phosphatase. The PTEN protein negatively regulates cell migration and cell survival and induces a G1 cell cycle block via negative regulation of the phosphatidylinositol 3'-kinase/protein kinase B/Akt signaling pathway. PTEN is frequently mutated or deleted in both prostate cancer cell lines and primary prostate cancers. A murine polyclonal antiserum was raised against a glutathione S-transferase fusion polypeptide of the COOH terninus of PTEN. Archival paraffin tissue sections from 109 cases of resected prostate cancer were immunostained with the antiserum, using DU145 and PC-3 cells as positive and negative controls, respectively. PTEN expression was seen in the secretory cells. Cases were considered positive when granular cytoplasmic staining was seen in all tumor cells, mixed when areas of both positive and negative tumor cell clones were seen, and negative when adjacent benign prostate tissue but not tumor tissue showed positive staining. Seventeen cases (15.6%) of prostate cancer were positive, 70 cases (64.2%) were mixed, and 22 cases (20.2%) were negative. Total absence of PTEN expression correlated with the Gleason score (P = 0.0081) and correlated more significantly with a Gleason score of 7 or higher (P = 0.0004) and with advanced pathological stage (American Joint Committee on Cancer stages T3b and T4; P = 0.0078). Thus, loss of PTEN protein is correlated with pathological markers of poor prognosis in prostate cancer.
肿瘤抑制基因PTEN/MMAC - 1/TEP - 1（以下简称PTEN）定位于染色体10q23，编码一种双特异性磷酸酶。PTEN蛋白负向调节细胞迁移和细胞存活，并通过对磷脂酰肌醇3'-激酶/蛋白激酶B/Akt信号通路的负向调节诱导G1期细胞周期阻滞。在前列腺癌细胞系和原发性前列腺癌中，PTEN经常发生突变或缺失。制备了一种针对PTEN羧基末端谷胱甘肽S - 转移酶融合多肽的鼠多克隆抗血清。使用DU145和PC - 3细胞分别作为阳性和阴性对照，用该抗血清对109例切除的前列腺癌存档石蜡组织切片进行免疫染色。在分泌细胞中可见PTEN表达。当在所有肿瘤细胞中均可见颗粒状细胞质染色时，病例被视为阳性；当同时可见阳性和阴性肿瘤细胞克隆区域时，病例被视为混合性；当相邻良性前列腺组织而非肿瘤组织显示阳性染色时，病例被视为阴性。17例（15.6%）前列腺癌病例为阳性，70例（64.2%）为混合性，22例（20.2%）为阴性。PTEN表达完全缺失与Gleason评分相关（P = 0.0081），与Gleason评分为7或更高相关更显著（P = 0.0004），并与晚期病理分期（美国癌症联合委员会分期T3b和T4；P = 0.0078）相关。因此，PTEN蛋白缺失与前列腺癌预后不良的病理标志物相关。
