Electron microscopy evidence that cytoplasmic localization of the p16INK4A "nuclear" cyclin-dependent kinase inhibitor (CKI) in tumor cells is specific and not an artifact.: A study in non-small cell lung carcinomas
Electron microscopy evidence that cytoplasmic localization of the p16INK4A "nuclear" cyclin-dependent kinase inhibitor (CKI) in tumor cells is specific and not an artifact.: A study in non-small cell lung carcinomas
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DOI：
10.1080/10520290310001659466
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发表时间：
2004-02-01
影响因子：
1.6
通讯作者：
Gorgoulis, VG
中科院分区：
文献类型：
--
作者：
Evangelou, K;Bramis, J;Gorgoulis, VG
\|众所周知，p16(INK4A) 蛋白在细胞核中充当细胞周期抑制剂。因此，p16 INKS 的细胞质定位通常被研究人员视为非特异性而忽略。最近的三项研究报告的结果与当前有关 p16(INK4A) 免疫组织化学定位的观点不同。这三者均证明表达细胞质 p16 (INK4A) 的乳腺癌和结肠癌代表不同的生物学亚群。我们之前在一定比例的非小细胞肺癌中检测到同时进行核和细胞质 p16 (INK4A) 染色。鉴于有关乳腺癌和结肠癌的报道，我们对我们的病例进行了超微结构重新评估，以阐明 p16（INK4A）细胞质表达的特异性。我们在部分肿瘤细胞的细胞核和细胞质中观察到 p16(INK4A) 免疫定位。在核质中检测到弥漫性致密核染色，而在粗面内质网附近的细胞质中观察到较弱的颗粒免疫反应性。阴性肿瘤细胞也可见。在肿瘤相关基质中，仅在细胞核中检测到细胞 p16(INK4A) 免疫反应性。我们已经证明 p16(INK4A) 细胞质染色是特异性的，并表明它代表了 p16(INK4A) 失活的机制，类似于在其他肿瘤抑制基因中观察到的机制。
\|It is well established that p16(INK4A) protein acts as a cell cycle inhibitor in the nucleus. Therefore, cytoplasmic localization of p16 INKS usually is disregarded by investigators as nonspecific. Three recent studies reported findings that differ from the current view concerning p16(INK4A) immunohistochemical localization. All three demonstrated that breast and colon cancers expressing cytoplasmic p16(INK4A) represent distinct biological subsets. We previously detected in a percentage of non-small cell lung carcinomas simultaneous nuclear and cytoplasmic p16(INK4A) staining. In view of the reports concerning breast and colon carcinomas, we conducted an ultrastructural re-evaluation of our cases to clarify the specificity of p16(INK4A) cytoplasmic expression. We observed p16(INK4A) immunolocalization in both the nucleus and the cytoplasm of a proportion of tumor cells. Diffuse dense nuclear staining was detected in the nucleoplasm, whereas weaker granular immunoreactivity was observed in the cytoplasm near the rough endoplasmic reticulum. Negative tumor cells also were visible. In the tumor-associated stromal, cells p16(INK4A) immunoreactivity was detected only in the nuclei. We have demonstrated that p16(INK4A) cytoplasmic staining is specific and suggest that it represents a mechanism of p16(INK4A) inactivation similar to that observed in other tumor suppressor genes.