Sood Ashwani K, Saxena Rakhee, Groth Jeff, Desouki Mohamed M, Cheewakriangkrai Chalong, Rodabaugh Kerry J, Kasyapa Chitta S, Geradts Joseph
Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Hum Pathol. 2007 Nov;38(11):1628-38. doi: 10.1016/j.humpath.2007.03.010. Epub 2007 May 22.
The purpose of this study was to understand the characteristics of prostate-derived Ets factor (PDEF) protein expression in breast and prostate cancer progression. A polyclonal antibody specific to PDEF was raised and reacted with tissue microarrays consisting of benign breast, in situ ductal, invasive ductal, and invasive lobular breast carcinomas. The antibody was also reacted with tissue microarrays, including benign prostate, prostate intraepithelial neoplasias (PINs), and prostate carcinomas. Increased expression of PDEF was identified in 18%, 50%, 46%, and 51% of benign breast tissues, intraductal, invasive ductal, and invasive lobular carcinomas, respectively. Importantly, in matched samples of benign breast vs tumor, 90% showed higher expression of PDEF in the tumor tissue. Moreover, in invasive breast carcinomas, increased PDEF expression tended to correlate with Her2/neu overexpression. Increased expression of PDEF was also found in 27%, 33%, and 40% of benign prostate tissues, PIN samples, and prostate adenocarcinomas, respectively. Again, in matching samples of cancer vs benign and cancer vs PIN, 68% and 70%, respectively, showed increased expression in the malignant tissue. Moreover, PDEF was found to be more highly expressed in tumors with intermediate or high Gleason score compared with low-grade tumors (P < .01). In addition, R1881 treatment induced PDEF expression in the LNCaP prostate tumor cell line, suggesting regulation of PDEF by androgens in vivo. Together, these results for the first time show frequent increased expression of PDEF protein in breast and prostate tumors and support a role for PDEF in breast and prostate cancer progression.
本研究的目的是了解前列腺源性Ets因子(PDEF)蛋白表达在乳腺癌和前列腺癌进展中的特征。制备了一种针对PDEF的多克隆抗体,并使其与由良性乳腺、原位导管癌、浸润性导管癌和浸润性小叶癌组成的组织芯片反应。该抗体还与包括良性前列腺、前列腺上皮内瘤变(PIN)和前列腺癌的组织芯片反应。在良性乳腺组织、导管内癌、浸润性导管癌和浸润性小叶癌中,PDEF表达增加的比例分别为18%、50%、46%和51%。重要的是,在良性乳腺与肿瘤的配对样本中,90%显示肿瘤组织中PDEF表达更高。此外,在浸润性乳腺癌中,PDEF表达增加往往与Her2/neu过表达相关。在良性前列腺组织、PIN样本和前列腺腺癌中,PDEF表达增加的比例分别为27%、33%和40%。同样,在癌与良性配对样本以及癌与PIN配对样本中,分别有68%和70%显示恶性组织中表达增加。此外,与低级别肿瘤相比,PDEF在Gleason评分中等或高的肿瘤中表达更高(P <.01)。此外,R1881处理诱导LNCaP前列腺肿瘤细胞系中PDEF表达,提示体内雄激素对PDEF的调节作用。总之,这些结果首次表明PDEF蛋白在乳腺和前列腺肿瘤中频繁表达增加,并支持PDEF在乳腺癌和前列腺癌进展中的作用。