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Inverse Correlation of Thioredoxin Expression with Estrogen Receptor- and p53-dependent Tumor Growth in Breast Cancer Tissues¹

Departments of Gastroenterological Surgery [Y. M., M. U., H. Ka., Y. Y.] and Pathology and Tumor Biology [R. T., K. Y.] and Division of the Science of Nursing [T. I.], Department of Biological Responses, Institute for Virus Research [H. N., J. Y.], Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan; Second Department of Surgery, Kagawa Medical University, Kagawa 760-0701, Japan [A. Y.]; First Department of Surgery, Ehime University School of Medicine, Ehime 791-0204, Japan [K. H.]; and Kodama Breast Clinic, Kyoto 606-8325, Japan [H. Ko.]

Estrogen receptor (ER) and p53 are important transcription factors in the growth regulation of tumor cells in breast cancer. We reported previously that thioredoxin (TRX) regulates the DNA binding activities of ER and p53 in vitro. The expression of pS-2, a trefoil factor, is also correlated with that of ER. To clarify the regulation mechanism of tumor growth in breast cancer, here we investigated the expression of TRX, ER, pS-2, and p53 and the mitotic index (MI) in 147 breast cancer tissues using immunohistochemical analysis. Of 123 TRX+ cases, ER+ cases (n = 62) showed a higher pS-2 score and lower MI than did ER- cases (n = 61). Furthermore, p53- cases (no mutation in p53; n = 76) also showed a lower MI than did p53+ cases (n = 47). There was no significant correlation between pS-2 and ER, MI and ER, or p53 and MI in the TRX- group. Among the ER+ and p53- cases (ER+/p53- group; n = 61), MI was lower in the TRX+ group (n = 46) than in the TRX- group (n = 15). However, in all other groups (n = 86) with abnormalities in the immunohistochemical expression of either p53 or ER, there was no significant correlation between MI and TRX expression. In the TRX+ and ER +/p53- group (n = 46), histological grading was lower than that in all other groups (n = 101). These findings suggest that TRX expression is linked to the ER- and p53-dependent regulation of tumor growth in breast cancer. In addition, TRX expression in ER+ and p53 intact (wild-type p53+) groups may mean better prognosis than in other conditions.

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