Anti-apoptotic role of the sonic hedgehog signaling pathway in the proliferation of ameloblastoma

Shiori Kanda, Takeshi Mitsuyasu, Yu Nakao, Shintarou Kawano, Yuichi Goto, Ryota Matsubara, Seiji Nakamura

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Abstract

Sonic hedgehog (SHH) signaling pathway is crucial to growth and patterning during organogenesis. Aberrant activation of the SHH signaling pathway can result in tumor formation. We examined the expression of SHH signaling molecules and investigated the involvement of the SHH pathway in the proliferation of ameloblastoma, the most common benign tumor of the jaws. We used immunohistochemistry on ameloblastoma specimens and immunocytochemistry and reverse transcription-PCR on the ameloblastoma cell line AM-1. We also used the inhibitors of SHH signaling, SHH neutralizing antibody and cyclopamine, to assess the effects of SHH on the proliferation of AM-1 cells. We detected expression of SHH, patched, GLI1, GLI2 and GLI3 in the ameloblastoma specimens and AM-1 cells. The proliferation of these cells was significantly inhibited in the presence of SHH neutralizing antibody or cyclopamine; this was confirmed by BrdU incorporation assays. Furthermore, in the presence of SHH neutralizing antibody, nuclear translocation of GLI1 and GLI2 was abolished, apoptosis was induced, BCL-2 expression decreased and BAX expression increased. Our results suggest that the SHH signaling pathway is constitutively active in ameloblastoma and plays an anti-apoptotic role in the proliferation of ameloblastoma cells through autocrine loop stimulation.

Original languageEnglish
Pages (from-to)695-702
Number of pages8
JournalInternational journal of oncology
Volume43
Issue number3
DOIs
Publication statusPublished - Sep 1 2013

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Ameloblastoma
Neutralizing Antibodies
Immunohistochemistry
Cell Proliferation
Organogenesis
Bromodeoxyuridine
Jaw
Reverse Transcription
Neoplasms
Apoptosis
Cell Line
Polymerase Chain Reaction
Growth

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Anti-apoptotic role of the sonic hedgehog signaling pathway in the proliferation of ameloblastoma. / Kanda, Shiori; Mitsuyasu, Takeshi; Nakao, Yu; Kawano, Shintarou; Goto, Yuichi; Matsubara, Ryota; Nakamura, Seiji.

In: International journal of oncology, Vol. 43, No. 3, 01.09.2013, p. 695-702.

Research output: Contribution to journalArticle

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