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Published on: August 21, 2013

A role of PDGFRalpha in basal cell carcinoma proliferation

J Xie1, M Aszterbaum, X Zhang

  • 1Cancer Research Institute, and Department of Dermatology, University of California, San Francisco, CA 94115, USA. jinxie@utmb.edu

Proceedings of the National Academy of Sciences of the United States of America
|August 2, 2001
PubMed

Insights

Activation of the hedgehog pathway in basal cell carcinoma (BCC) drives platelet-derived growth factor receptor alpha (PDGFRalpha) expression. This PDGFRalpha up-regulation promotes cancer cell proliferation, offering a new therapeutic target for BCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Dermatology

Background:

  • Basal cell carcinoma (BCC) is the most common human cancer, frequently driven by hedgehog pathway activation.
  • The precise molecular mechanisms linking hedgehog pathway activation to BCC development remain unclear.

Purpose of the Study:

  • To elucidate the molecular mediators of hedgehog pathway-driven oncogenesis in BCC.
  • To investigate the role of Gli1 in regulating downstream targets involved in BCC proliferation.

Main Methods:

  • Investigated Gli1-mediated activation of platelet-derived growth factor receptor alpha (PDGFRalpha) in C3H10T(1/2) cells.
  • Analyzed the activation of the ras-ERK pathway downstream of PDGFRalpha.
  • Examined PDGFRalpha expression in murine and human BCC samples.
  • Assessed the impact of Patched (PTC) re-expression and PDGFRalpha inhibition on BCC proliferation in vitro.

Main Results:

  • Gli1 was shown to activate PDGFRalpha, leading to ras-ERK pathway activation and promoting cell proliferation.
  • High PDGFRalpha expression was observed in both murine and human BCCs.
  • Re-expression of PTC or inhibition of PDGFRalpha significantly reduced proliferation in a murine BCC cell line.

Conclusions:

  • Increased PDGFRalpha expression is a key mechanism by which hedgehog pathway mutations contribute to BCC.
  • Targeting PDGFRalpha represents a potential therapeutic strategy for basal cell carcinoma.

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