Aberrant Expression of the Cell Polarity Regulator aPKC&lgr;/&igr; is Associated With Disease Progression in Cervical Intraepithelial Neoplasia (CIN): A Possible Marker for Predicting CIN Prognosis
Aberrant Expression of the Cell Polarity Regulator aPKC&lgr;/&igr; is Associated With Disease Progression in Cervical Intraepithelial Neoplasia (CIN): A Possible Marker for Predicting CIN Prognosis
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细胞极性调节因子 aPKC 的异常表达
DOI：
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发表时间：
2016
影响因子：
2.4
通讯作者：
E. Miyagi
中科院分区：
文献类型：
--
作者：
T. Mizushima;M. Asai;K. Akimoto;Y. Nagashima;M. Taguri;K. Sasaki;M. Nakaya;R. Asano;Aya Tokinaga;T. Kiyono;F. Hirahara;S. Ohno;E. Miyagi
非典型蛋白激酶C &lgr /&igr；（aPKC&lgr;/&igr;）是上皮细胞极性的调节因子。它也在一些癌症中过度表达，并在细胞增殖和侵袭中起作用。因此，我们假设aPKC&lgr；/&igr；可能参与宫颈上皮内瘤变（CIN）的发生和发展，CIN是由人乳头瘤病毒引起的宫颈癌癌前病变。为此，我们研究了aPKC&lgr；/&igr；表达和CIN。aPKC&lgr; / &igr;应用免疫组织化学方法评估192例CIN活检样本和13例正常上皮样本的表达水平和亚细胞定位。aPKC&lgr; / &igr;过表达（正常上皮，7.7%;CIN1, 41.7%; CIN2/3, 76.4%）和aPKC&lgr；/&igr；细胞核定位（正常上皮，0.0%;CIN1, 36.9%; CIN2/3, 78.7%）在CIN标本中高于正常标本（P<0.05），提示CIN分级与aPKC&lgr；/&igr；过表达和核定位。然后，使用Cox比例风险模型回顾性分析140例CIN病例的4年累积疾病进展和消退率。CIN1例aPKC&lgr；/&igr；aPKC&lgr;/&igr；与aPKC&lgr /&igr正常的CIN1病例相比，核定位的进展率更高；表达水平或细胞质定位（分别为62.5%比9.7%和63.1%比9.4%，P<0.001）。多因素分析显示，16型和18型人乳头瘤病毒aPKC&lgr /&igr；过表达（风险比=4.26；95%可信区间为1.50-12.1；P=0.007）和aPKC&lgr；/&igr；核定位（风险比为3.59；95%可信区间为1.24-10.4；P=0.019）是CIN1进展的独立危险因素。综上，aPKC&lgr;/&igr；可用于CIN患者的治疗管理，特别是那些非人类乳头瘤病毒16/18型。
Atypical protein kinase C &lgr;/&igr; (aPKC&lgr;/&igr;) is a regulator of epithelial cellular polarity. It is also overexpressed in several cancers and functions in cell proliferation and invasion. Therefore, we hypothesized that aPKC&lgr;/&igr; may be involved in development and progression of cervical intraepithelial neoplasia (CIN), the precancerous disease of cervical cancer induced by human papillomavirus. To do this, we investigated the relationship between aPKC&lgr;/&igr; expression and CIN. aPKC&lgr;/&igr; expression level and subcellular localization were assessed in 192 CIN biopsy samples and 13 normal epithelial samples using immunohistochemistry. aPKC&lgr;/&igr; overexpression (normal epithelium, 7.7%; CIN1, 41.7%; CIN2/3, 76.4%) and aPKC&lgr;/&igr; nuclear localization (normal epithelium, 0.0%; CIN1, 36.9%; CIN2/3, 78.7%) were higher in CIN samples than normal samples (P<0.05), suggesting that CIN grade is related to aPKC&lgr;/&igr; overexpression and nuclear localization. Then, 140 CIN cases were retrospectively analyzed for 4-yr cumulative disease progression and regression rates using the Cox proportional hazards model. CIN1 cases with aPKC&lgr;/&igr; overexpression or aPKC&lgr;/&igr; nuclear localization had a higher progression rate than CIN1 cases with normal aPKC&lgr;/&igr; expression levels or cytoplasmic localization (62.5% vs. 9.7% and 63.1% vs. 9.4%, respectively; P<0.001). Multivariate analysis indicated that human papillomavirus types 16 and 18, aPKC&lgr;/&igr; overexpression (hazard ratio=4.26; 95% confidence interval, 1.50–12.1; P=0.007), and aPKC&lgr;/&igr; nuclear localization (hazard ratio=3.59; 95% confidence interval, 1.24–10.4; P=0.019) were independent risk factors for CIN1 progression. In conclusion, aPKC&lgr;/&igr; could be useful for the therapeutic management of patients with CIN, particularly those with non-human papillomavirus 16/18 types.
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影响因子：
11.2
作者：
R. P. Regala;Capella R. Weems;L. Jamieson;A. Khoor;E. Edell;C. Lohse;A. Fields
通讯作者：
R. P. Regala;Capella R. Weems;L. Jamieson;A. Khoor;E. Edell;C. Lohse;A. Fields
影响因子：
11.2
作者：
Lin Zhang;Jia Huang;N. Yang;Shun Liang;A. Barchetti;Antonis Giannakakis;Mark G. Cadungog;A. O’Brien-Jenkins;M. Massobrio;K. Roby;D. Katsaros;P. Gimotty;R. Butzow;B. Weber;G. Coukos
通讯作者：
Lin Zhang;Jia Huang;N. Yang;Shun Liang;A. Barchetti;Antonis Giannakakis;Mark G. Cadungog;A. O’Brien-Jenkins;M. Massobrio;K. Roby;D. Katsaros;P. Gimotty;R. Butzow;B. Weber;G. Coukos
DOI：
10.1073/pnas.0505641102
发表时间：
2005-08-30
影响因子：
11.1
作者：
Eder, AM;Sui, XM;Mills, GB
通讯作者：
Mills, GB
影响因子：
2.7
作者：
A. Suzuki;K. Akimoto;S. Ohno
通讯作者：
A. Suzuki;K. Akimoto;S. Ohno
非典型蛋白激酶Cι作为人类癌基因和治疗靶标。
影响因子：
5.8
作者：
Parker, Peter J.;Justilien, Verline;Riou, Philippe;Linch, Mark;Fields, Alan P.
通讯作者：
Fields, Alan P.