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[Cancer Research 64, 6071-6074, September 1, 2004]
© 2004 American Association for Cancer Research

Regular Articles

Hedgehog Signaling Pathway is a New Therapeutic Target for Patients with Breast Cancer

Makoto Kubo1, Masafumi Nakamura1, Akira Tasaki1, Naoki Yamanaka1, Hiroshi Nakashima1, Masatoshi Nomura2, Syoji Kuroki3 and Mitsuo Katano1

Departments of 1 Cancer Therapy and Research, 2 Medicine and Bioregulatory Science, and 3 Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

The Hedgehog (Hh) signaling pathway functions as an organizer in embryonic development. Genetic analysis has demonstrated a critical role for the Hh pathway in mammary gland morphogenesis. Disruption of Patched1, a component of the Hh pathway, results in abnormal growth of mammary duct. Recent studies have shown constitutive activation of the Hh pathway in various types of malignancies. However, it remains unclear whether this pathway is activated in human breast cancer. Here, we determined the expression of the components, including Sonic Hh, Patched1, and Gli1, of the Hh pathway by immunohistochemical staining in a series of 52 human breast carcinomas. All of 52 tumors display staining of high intensity for Gli1 when compared with adjacent normal tissue. The nuclear staining ratio of Gli1 correlates with expression of estrogen receptor and histologic type. Exposure to cyclopamine, a steroidal alkaloid that blocks the Hh pathway, suppresses expression of Gli1 and the growth of the Hh pathway-activated breast carcinoma cells. These data indicate that the Hh pathway is a new candidate for therapeutic target of breast cancer.




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