探討絲胺酸727 磷酸化的STAT3（Signal Transducer and Activator of transcription 3在子宮頸上皮內贅瘤上的表現及其可能扮演的角色

The Expression and Possible Roles of p-STAT3 (ser 727) in Cervical Intraepithelial Neoplasia

楊曉芳(Sheau-Fang Yang)

指導教授 ： 蔡志仁

高雄醫學大學/醫學院/醫學研究所/碩士(2004年)

摘要

目的：STAT3（signal transducer and activator of transcription 3）近
年來被認為是一種致癌基因，在很多癌症上都可看到它表現出持續活
化的現象。有關STAT3 酪胺酸磷酸化的研究很多，但目前對STAT3
絲胺酸磷酸化的部分仍不太了解。本實驗的研究目的是觀察在絲胺酸
727 位置上磷酸化的STAT3（p-STAT3 (ser 727)）及STAT3 在子宮頸
上皮內贅瘤的表現，並探討其表現與細胞異生的程度及Ki-67 表現程
度的相關性，進一步研究其在子宮頸上皮內贅瘤演進成侵襲性子宮頸
癌的過程中可能扮演的角色。
材料及方法：蒐集石臘包埋的標本共83 例，含20 例CIN 1、10
例CIN 2、26 例CIN 3、10 例正常子宮頸組織及17 例鱗狀細胞癌，進
行p-STAT3 (ser 727)與STAT3 的免疫組織化學染色，觀察它們染色的
位置及表現量，並以半定量的方式紀錄其表現量。最後再和Ki-67 的
免疫組織化學染色結果作比對。
結果：p-STAT3 (ser 727)在細胞核和細胞質的染色結果以及STAT3
在細胞質的表現量上，CIN 3 確實比CIN 1/2 有更高比例呈現高度表
現，且具有統計上的意義（p < 0.001，p < 0.001，p = 0.003）。另外與
正常子宮頸和鱗狀細胞癌的組織作比對，的確發現p-STAT3 (ser 727)
和STAT3 在正常子宮頸上皮幾乎不表現，在鱗狀細胞癌的細胞核及細
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胞質上表現量則很高。分析結果發現p-STAT3 (ser 727)和STAT3 在核
及質的表現量與Ki-67 在核的表現量有統計上的意義（p < 0.001, p <
0.001, p = 0.025, p = 0.030）。
結論：本篇是第一篇研究在子宮頸上皮內贅瘤上p-STAT3 (ser 727)
和STAT3 表現程度的論文。我們認為在子宮頸上皮內贅瘤中STAT3
是持續活化的，而p-STAT3 (ser 727)在細胞增生和異生的進展上扮演
了一個關鍵的角色。在子宮頸上皮內贅瘤中，p-STAT3 (ser 727)的表現
量可用來作為一個增生的生物指標，同時可監測子宮頸上皮內贅瘤的
進展，並可在開發抗子宮頸癌的藥物上提供更有用的資訊。

關鍵字

子宮頸癌 ； 鱗狀細胞癌 ； 子宮頸上皮內贅瘤 ； STAT3 ； p-STAT3

並列摘要

Purpose: Signal transducer and activator of transcription 3 (STAT3)
has recently been classified as an oncogene, and STAT3 protein
constitutive activation was detected in many cancers. However, in contrast
to the more well-characterized events of STAT3 activation by tyrosine
phosphorylation, regulation of STATs by serine phosphorylation is
understood less. The purpose of this study was to evaluate the expression
patterns of phospho-serine residue 727 (p-STAT3 (ser 727)) as well as
STAT3 in cervical intraepithelial neoplasia (CIN), and to identify the
possible role of p-STAT3 (ser 727) in CIN and cervical tumorgenesis.
Experimental design: Paraffin-embedded sections from 83 patients
including 20 CIN 1, 10 CIN 2, 26 CIN 3, 10 normal cervical epithelium
and 17 squamous cell carcinoma (SCC) were collected for this study.
Immunohistochemical analysis was performed and the expression and
location of p-STAT3 (ser 727) and STAT3 were evaluated. The results
were categorized by semiquantitative method and correlated with Ki-67
expression.
Results: The proportion of p-STAT3 (ser 727) high-level expressions
in nuclei and cytoplasm and of STAT3 high-level expression in cytoplasm
were significantly higher in CIN 3 (76.92%, 69.23%, 57.69%) than in CIN
1/2 (13.33%, 13.33%, 16.67%) (p < 0.001, p < 0.001, p = 0.003). In
addition, there was no or little expression of p-STAT3 (ser 727) and
STAT3 in normal cervical epithelium, while increased immunostaining of
p-STAT3 (ser 727) and STAT3 was present in SCC. The nuclear and
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cytoplasmic presentations of p-STAT3 (ser 727) and STAT3 were
correlated with K-67 nuclear presentation (p < 0.001, p < 0.001, p = 0.025,
p = 0.030).
Conclusion: This is the first study to establish the expression profiles
of p-STAT3 (ser 727) and STAT3 in CIN. We propose that STAT3
signaling pathway and its aberrant serine phosphorylation are correlated
with cell proliferation and may play a crucial role in progression of CIN
and carcinogenesis of cervical cancer. We believe the accomplishment of
this project will provide a better understanding of the carcinogenesis of
cervical cancer and provide useful information for the discovery of
potential anti-cervical cancer drugs.

並列關鍵字

cervical cancer ； squamous cell carcinoma ； STAT3 ； cervical intraepithelial neoplasia ； p-STAT3 (ser 727)

參考文獻

AJCC (2002). AJCC Cancer Staging Manual. 6th ed. Springer Verlag: New

York.

Akira S (2000). Roles of STAT3 defined by tissue-specific gene targeting.

Oncogene 19:2607-11.

Bacus JW, Boone CW, Bacus JV, Follen M, Kelloff GJ, Kagan V, Lippman