Expression and colocalization of β-catenin and lymphoid enhancing factor-1 in prostate cancer progression.
Expression and colocalization of β-catenin and lymphoid enhancing factor-1 in prostate cancer progression.
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DOI：
10.1016/j.humpath.2015.12.024
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发表时间：
2016-05
期刊：
影响因子：
3.3
通讯作者：
Ricke WA
中科院分区：
文献类型：
--
作者：
Bauman TM;Vezina CM;Ricke EA;Halberg RB;Huang W;Peterson RE;Ricke WA
本研究的目的是客观地研究良性和分期前列腺癌（PCa）标本中β-catenin和LEF1的丰度、亚细胞定位和共定位。采用多路免疫组化技术对组织芯片进行染色，该芯片包含肿瘤邻近组织良性前列腺组织（BPT， 48例）、高级别前列腺上皮内瘤变（HGPIN， 25例）、局部PCa（42例）、侵袭性PCa（31例）和转移性PCa（22例），其中含有E-cadherin、β-catenin和LEF1抗体。使用多光谱成像进行定量，并评估前列腺癌进展过程中的蛋白表达和共定位。HGPIN和PCa的间质核β-catenin丰度均高于BPT (p<0.05)，转移性PCa的上皮核β-catenin丰度均低于BPT （p<0.05）。与BPT相比，HGPIN中上皮和间质核LEF1的丰度更高，而转移瘤中上皮核LEF1的丰度也更高。与BPT相比，HGPIN中上皮和间质核双阳性β-cat+/LEF1+细胞的比例更高。此外，与BPT相比，上皮细胞β-cat+/LEF1+细胞在局部PCa和转移中的比例更高。大量基质细胞LEF1阳性，而β-catenin不阳性。β-catenin与LEF1丰度在上皮中呈负相关（p<0.0001），而在基质中无显著相关性（p< 0.05）。我们得出结论，相对于BPT， β-catenin和LEF1的共定位在HGPIN和转移中增加，表明β-catenin-LEF1介导的转录在PCa的恶性转化和转移中都有作用。此外，我们的研究结果表明，LEF1丰度本身并不是前列腺组织中β-catenin活性的可靠读数。
The purpose of this study was to objectively investigate β-catenin and LEF1 abundance, subcellular localization, and co-localization across benign and staged prostate cancer (PCa) specimens. A tissue microarray containing tumor-adjacent histologically benign prostate tissue (BPT; n=48 patients), high-grade prostatic intraepithelial neoplasia (HGPIN; n=25), localized PCa (n=42), aggressive PCa (n=31), and metastases (n=22) was stained using multiplexed immunohistochemistry with antibodies towards E-cadherin, β-catenin, and LEF1. Multispectral imaging was used for quantitation, and protein expression and co-localization was evaluated across prostate cancer progression. Stromal nuclear β-catenin abundance was greater in HGPIN and PCa compared to BPT (p<0.05 for both), and epithelial nuclear β-catenin abundance was lower in metastatic PCa than BPT (p<0.05 for both). Epithelial and stromal nuclear LEF1 abundance was greater in HGPIN compared to BPT, while epithelial nuclear LEF1 was also greater in metastases. The proportion of epithelial and stromal nuclear double positive β-cat+/LEF1+ cells was greater in HGPIN compared to BPT. Additionally, the proportion of epithelial β-cat+/LEF1+ cells was greater in localized PCa and metastases compared to BPT. A significant amount of stromal cells were positive for LEF1 but not β-catenin. β-catenin and LEF1 abundance were negatively correlated in the epithelium (p<0.0001) but not the stroma (p>0.05). We conclude that β-catenin and LEF1 co-localization is increased in HGPIN and metastasis relative to BPT, suggesting a role for β-catenin-LEF1-mediated transcription in both malignant transformation and metastasis of PCa. Further, our results suggest that LEF1 abundance alone is not a reliable readout for β-catenin activity in prostate tissues.