STAT3 ser727 phosphorylation and its association with negative estrogen receptor status in breast infiltrating ductal carcinoma

Authors

  • Yao-Tsung Yeh,

    1. Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China
    2. Department of Medical Research, E-DA Hospital, I-Shou University, Taiwan, Republic of China
    3. Department of Obstetrics and Gynecology, E-DA Hospital, I-Shou University, Taiwan, Republic of China
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  • Fu Ou-Yang,

    1. Department of Surgery, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China
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  • I-Fen Chen,

    1. Department of Medical Research, E-DA Hospital, I-Shou University, Taiwan, Republic of China
    2. Department of Obstetrics and Gynecology, E-DA Hospital, I-Shou University, Taiwan, Republic of China
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  • Sheau-Fang Yang,

    1. Department of Pathology, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China
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  • Yuan-Yung Wang,

    1. Department of Pathology, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China
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  • Hung-Yi Chuang,

    1. Department of Clinical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Republic of China
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  • Jinu-Huang Su,

    1. Department of Obstetrics and Gynecology, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China
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  • Ming-Feng Hou,

    1. Department of Obstetrics and Gynecology, E-DA Hospital, I-Shou University, Taiwan, Republic of China
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  • Shyng-Shiou F. Yuan

    Corresponding author
    1. Department of Medical Research, E-DA Hospital, I-Shou University, Taiwan, Republic of China
    2. Department of Clinical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Republic of China
    • Department of Obstetrics and Gynecology, E-DA Hospital, I-Shou University, Kaohsiung County, Taiwan 824, Republic of China
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Abstract

Although it is known that STAT3 transcriptional activity is modulated by phosphorylation at serine residue 727, the role of STAT3 serine phosphorylation in breast cancer remains mostly unexplored. In this study, we examined the expression patterns of serine residue 727-phosphorylated STAT3 (p-ser727-STAT3) in breast infiltrating ductal carcinoma tissues and nearby noncancer tissues by using immunoblotting techniques, and correlated the expression profiles with clinicopathological characteristics. A significantly elevated p-ser727-STAT3 expression was observed in 61.8% (42/68) of breast cancer tissues as compared to corresponding noncancer tissues (p < 0.001). Further, immunohistochemical analysis also showed an increased nuclear p-ser727-STAT3 staining in cancer lesions. The increased p-ser727-STAT3 expression in breast infiltrating ductal carcinoma tissues correlated significantly with negative estrogen receptor (ER) status, increased stage of cancer and increased tumor size (p = 0.001, 0.024 and 0.014, individually). Intriguingly, we noticed that the expression levels of p-ser727-STAT3 in ER-negative breast cancer cell lines were higher than those in ER-positive breast cancer cell lines. In ER-positive MCF7 cells, treatment with ERα-specific siRNA increased, whereas treatment with anticancer drug tamoxifen decreased the expression of p-ser727-STAT3, phenomena not observed in ER-negative MDA-MB-231 cells. In conclusion, our results suggest that p-ser727-STAT3 may be involved in the pathogenesis of breast cancer in an ER-dependent manner. © 2006 Wiley-Liss, Inc.

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