Delgado L, Gärtner F, Dias Pereira P
Instituto de Ciências Biomédicas Abel Salazar, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira n° 228, Porto, Portugal.
Instituto de Ciências Biomédicas Abel Salazar, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira n° 228, Porto, Portugal; Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Rua Dr. Roberto Frias, Porto, Portugal.
J Comp Pathol. 2015 Feb-Apr;152(2-3):138-44. doi: 10.1016/j.jcpa.2014.12.004. Epub 2015 Feb 7.
Mammalian target of rapamycin (mTOR) is a serine-threonine kinase involved in cell growth, proliferation and survival. Activation of mTOR has been reported in various tumour types, including human breast cancer; however, the expression of mTOR in canine mammary tumours has not been examined. In the present study, expression of the activated form of mTOR (phospho-mTOR [p-mTOR]) was examined immunohistochemically in five normal canine mammary glands, 45 canine mammary carcinomas and their corresponding metastatic lesions (n = 15). Phospho-mTOR was not expressed in normal canine mammary tissue, but cytoplasmic labelling was observed in 78% of canine mammary carcinomas. Two carcinomas had both cytoplasmic and nuclear labelling. No significant relationship was found between p-mTOR cytoplasmic expression and histological type or grading of carcinomas, degree of tubular formation, anisokaryosis, mitotic activity or lymph node metastasis. In all except one case, the expression pattern of p-mTOR in lymph node metastases was similar or decreased when compared with the primary lesion. The findings suggest that p-mTOR is involved in mammary carcinogenesis in dogs. However, p-mTOR cytoplasmic expression does not appear to be a prognostic indicator in canine mammary carcinomas, which may be related to its subcellular location in the neoplastic cells. Canine mammary tumours may provide a model for the development of innovative medical strategies involving mTOR inhibitors in human breast cancer.
雷帕霉素哺乳动物靶点（mTOR）是一种丝氨酸 - 苏氨酸激酶，参与细胞生长、增殖和存活。在包括人类乳腺癌在内的各种肿瘤类型中均有mTOR激活的报道；然而，mTOR在犬乳腺肿瘤中的表达尚未被研究。在本研究中，采用免疫组织化学方法检测了5个正常犬乳腺、45个犬乳腺癌及其相应转移灶（n = 15）中mTOR激活形式（磷酸化mTOR [p - mTOR]）的表达。p - mTOR在正常犬乳腺组织中不表达，但在78%的犬乳腺癌中观察到细胞质标记。有两个癌同时有细胞质和细胞核标记。p - mTOR的细胞质表达与癌的组织学类型或分级、管状形成程度、核异形性、有丝分裂活性或淋巴结转移之间未发现显著相关性。除1例以外，在所有病例中，与原发灶相比，p - mTOR在淋巴结转移灶中的表达模式相似或降低。这些发现表明p - mTOR参与犬乳腺肿瘤的发生。然而，p - mTOR的细胞质表达似乎不是犬乳腺癌的预后指标，这可能与其在肿瘤细胞中的亚细胞定位有关。犬乳腺肿瘤可能为开发涉及mTOR抑制剂的人类乳腺癌创新治疗策略提供一个模型。
