Increased expression of the hedgehog signaling pathway in pediatric solid malignancies

Oue, Takaharu; Yoneda, Akihiro; Uehara, Shuichiro; Yamanaka, Hiroaki; Fukuzawa, Masahiro

doi:10.1016/j.jpedsurg.2009.10.081

Cited by 62 publications

(50 citation statements)

References 21 publications

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“…In the present study, real-time PCR revealed that SHH, DHH, IHH, PTCH1, SMO, GLI1, GLI2, and ULK3 transcripts were over-expressed in rhabdomyosarcoma cell lines and biopsy specimens. Recently, it has been reported that human rhabdomyosarcoma specimens express SHH, PTCH1, GLI1, and GLI3 (19,20). Their findings are compatible with our real-time PCR results.…”

Section: Discussionsupporting

confidence: 92%

Pharmacological inhibition of the Hedgehog pathway prevents human rhabdomyosarcoma cell growth

Kawabata

Ijiri²,

Ishidou³

et al. 2011

Int J Oncol

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Abstract. The Hedgehog pathway functions as an organizer in embryonic development. Recent studies have shown that mutation of the PTCH1 gene involved in the Hedgehog pathway affects rhabdomyosarcoma development. However, the expression of Hedgehog pathway molecules in human rhabdomyosarcoma cells has not been well clarified. In addition, the effect of pharmacological inhibition of the Hedgehog pathway is not known. We investigated the expression of the genes involved in the Hedgehog pathway using human rhabdomyosarcoma cell lines and biopsy specimens. Further, we evaluated the effect of pharmacological inhibition of the Hedgehog pathway using cyclopamine or GANT61 by WST assay, cell proliferation assay and cell death detection assay. Real-time PCR revealed that human rhabdomyosarcoma cell lines and biopsy specimens overexpressed the following genes: Sonic hedgehog, Indian hedgehog, Desert hedgehog, PTCH1, SMO, GLI1, GLI2 and ULK3. Immunohistochemistry revealed that rhabdomyosarcoma cell lines and biopsy specimens expressed SMO and GLI2. Inhibition of SMO by cyclopamine slowed the growth of human rhabdomyosarcoma cell lines. Similarly, inhibition of GLI by GANT61 slowed the growth of human rhabdomyosarcoma cell lines. Inhibition of cell proliferation and apoptotic cell death together prevented the growth of rhabdomyosarcoma cells by cyclopamine and GANT61 treatment. Our findings suggest that pharmacological inhibition of the Hedgehog pathway may be a useful approach for treating rhabdomyosarcoma patients.

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Section: Discussionsupporting

confidence: 92%

Pharmacological inhibition of the Hedgehog pathway prevents human rhabdomyosarcoma cell growth

Kawabata

Ijiri²,

Ishidou³

et al. 2011

Int J Oncol

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“…In addition to genetic alterations, ligand-dependent stimulation of Hh signaling has recently been shown to promote tumor cell growth in different types of human cancers (Berman et al, 2002Thayer et al, 2003;Watkins et al, 2003;Karhadkar et al, 2004;Scales and de Sauvage, 2009). In RMS, aberrant activation of the Hh cascade has been detected in primary specimens and has been attributed to genetic inactivation of Ptch1 or of suppressor of fused (SUFU), like Ptch1, a negative regulator of Hh signaling, or to Gli1 amplification (Roberts et al, 1989;Khatib et al, 1993;Ragazzini et al, 2004;Tostar et al, 2006;Oue et al, 2010). Ptch1 heterozygous mice have been shown to develop RMS resembling the embryonal subtype (Hahn et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Activation of the hedgehog pathway confers a poor prognosis in embryonal and fusion gene-negative alveolar rhabdomyosarcoma

et al. 2010

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“…In rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, HH signaling is preferentially activated in specific subgroups of RMS. [236][237][238][239] Ptch1, Gli1, and Gli3 are expressed at significant higher levels in embryonal RMS than in fusion-gene negative alveolar RMS than in fusion-gene positive alveolar RMS. High expression of Ptch1 significantly correlated with reduced cumulative survival.…”

Section: Stem Cell Pathwaysmentioning

confidence: 97%

Novel Therapeutic Targets in Soft Tissue Sarcomas

Chu¹,

Mulder²

2011

Soft Tissue Tumors

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Increased expression of the hedgehog signaling pathway in pediatric solid malignancies

Cited by 62 publications

References 21 publications

Pharmacological inhibition of the Hedgehog pathway prevents human rhabdomyosarcoma cell growth

Pharmacological inhibition of the Hedgehog pathway prevents human rhabdomyosarcoma cell growth

Activation of the hedgehog pathway confers a poor prognosis in embryonal and fusion gene-negative alveolar rhabdomyosarcoma

Novel Therapeutic Targets in Soft Tissue Sarcomas

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