Falasca Laura, Torino Francesco, Marconi Matteo, Costantini Manuela, Pompeo Vincenzo, Sentinelli Steno, De Salvo Laura, Patrizio Mario, Padula Cristiano, Gallucci Michele, Piacentini Mauro, Malorni Walter
Laboratory of Cell Biology and Electron Microscopy, National Institute for Infectious Diseases I.R.C.C.S. 'L. Spallanzani', Rome, Italy.
Department of Systems Medicine, Chair of Medical Oncology, Tor Vergata University of Rome, Rome, Italy.
Apoptosis. 2015 Dec;20(12):1577-86. doi: 10.1007/s10495-015-1176-3.
Prostate cancer is among the most commonly diagnosed male diseases and a leading cause of cancer mortality in men. There is emerging evidence that autophagy plays an important role in malignant cell survival and offers protection from the anti-cancer drugs in prostate cancer cells. AMBRA1 and the autophagic protein sequestosome-1 (SQSTM1; p62) expression were evaluated by immunohistochemistry and western blot on tissue samples from both benign and malignant prostatic lesions. The data reported in this pilot study demonstrated an increased expression of AMBRA1 and SQSTM1, which were also associated with an accumulation of LC3II in prostate cancer but not in benign lesion. In the present study we found that: (i) at variance with benign lesion, prostate cancer cells underwent SQSTM1 accumulation, i.e., clearly displayed a defective autophagic process but, also, (ii) prostate cancer accumulated AMBRA1 and (iii) this increase positively correlated with the Gleason score. These results underscore a possible implication of autophagy in prostate cancer phenotype and of AMBRA1 as possible cancer progression biomarker in this malignancy.
前列腺癌是最常被诊断出的男性疾病之一，也是男性癌症死亡的主要原因。新出现的证据表明，自噬在恶性细胞存活中起重要作用，并能保护前列腺癌细胞免受抗癌药物的影响。通过免疫组织化学和蛋白质印迹法对良性和恶性前列腺病变组织样本中的AMBRA1和自噬蛋白聚集体蛋白1（SQSTM1；p62）表达进行了评估。这项初步研究报告的数据表明，AMBRA1和SQSTM1表达增加，这也与前列腺癌中LC3II的积累有关，而在良性病变中则没有。在本研究中，我们发现：（i）与良性病变不同，前列腺癌细胞出现SQSTM1积累，即明显显示出自噬过程存在缺陷，而且，（ii）前列腺癌中AMBRA1积累，（iii）这种增加与Gleason评分呈正相关。这些结果强调了自噬在前列腺癌表型中的可能作用，以及AMBRA1作为这种恶性肿瘤中可能的癌症进展生物标志物的作用。
