Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer

Makoto Kubo, Masafumi Nakamura, Akira Tasaki, Naoki Yamanaka, Hiroshi Nakashima, Masatoshi Nomura, Syoji Kuroki, Mitsuo Katano

Research output: Contribution to journalArticle

353 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)6071-6074
Number of pages4
JournalCancer Research
Volume64
Issue number17
DOIs
Publication statusPublished - Sep 1 2004

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Breast Neoplasms
Staining and Labeling
Therapeutics
Human Mammary Glands
Growth
Morphogenesis
Alkaloids
Estrogen Receptors
Embryonic Development
Neoplasms
Breast
cyclopamine

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer. / Kubo, Makoto; Nakamura, Masafumi; Tasaki, Akira; Yamanaka, Naoki; Nakashima, Hiroshi; Nomura, Masatoshi; Kuroki, Syoji; Katano, Mitsuo.

In: Cancer Research, Vol. 64, No. 17, 01.09.2004, p. 6071-6074.

Research output: Contribution to journalArticle

Kubo, M, Nakamura, M, Tasaki, A, Yamanaka, N, Nakashima, H, Nomura, M, Kuroki, S & Katano, M 2004, 'Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer', Cancer Research, vol. 64, no. 17, pp. 6071-6074. https://doi.org/10.1158/0008-5472.CAN-04-0416
Kubo, Makoto ; Nakamura, Masafumi ; Tasaki, Akira ; Yamanaka, Naoki ; Nakashima, Hiroshi ; Nomura, Masatoshi ; Kuroki, Syoji ; Katano, Mitsuo. / Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer. In: Cancer Research. 2004 ; Vol. 64, No. 17. pp. 6071-6074.
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