Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Int J Biol Sci. 2010 Aug 8;6(5):428-42. doi: 10.7150/ijbs.6.428.
Our previous studies revealed that pregnancy associated breast cancer (PABC) had significantly reduced nuclear p63 expression in myoepithelia, while intense cytoplasmic p63 expression in associated epithelia. Our current study assessed these epithelia using immunohistochemistry with a panel of aggressiveness and invasiveness related markers and comparative genomic hybridization (array-CGH) with over 30,000 DNA probes. These epithelia showed several unique alterations, including (1) immunohistochemical and morphological resemblance to invasive cancer, (2) significant gain in copy numbers of DNA coding genes for morphogenesis, angiogenesis, and metastasis, and (3) significant loss in copy numbers of DNA coding genes for tumor suppressors, cell adhesion, and macromolecular complex assembly or intra-cellular trafficking. Detected array-CGH alterations correlated well with in vivo expression of a number of corresponding proteins tested. These findings suggest that aberrant sub-cellular localization of p63 expression in normal or hyperplastic appearing epithelial cells may significant contribute to increased invasiveness and aggressiveness of these cells.
我们之前的研究表明，妊娠相关性乳腺癌（PABC）在肌上皮中显著降低了核 p63 的表达，而在相关上皮中则强烈表达细胞质 p63。我们目前的研究使用一组与侵袭性和侵袭性相关的标志物进行免疫组织化学评估，并使用超过 30,000 个 DNA 探针进行比较基因组杂交（array-CGH）。这些上皮表现出多种独特的改变，包括（1）免疫组织化学和形态学上类似于浸润性癌，（2）形态发生、血管生成和转移的 DNA 编码基因的拷贝数显著增加，（3）肿瘤抑制基因、细胞黏附以及大分子复合物组装或细胞内运输的 DNA 编码基因的拷贝数显著减少。检测到的 array-CGH 改变与体内检测到的许多相应蛋白质的表达相关性良好。这些发现表明，p63 表达在正常或增生性上皮细胞中的亚细胞定位异常可能显著促进这些细胞的侵袭性和侵袭性。
