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Decreased expression of Apaf-1 with progression of melanoma

Rita Mustika1, Arief Budiyanto, Chikako Nishigori

  • 1Division of Dermatology, Clinical Molecular Medicine, Faculty of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.

Pigment Cell Research
|January 15, 2005
PubMed

Insights

Melanoma cells lose Apoptotic protease-activating factor-1 (Apaf-1) protein as tumors progress, leading to chemotherapy resistance. Reduced Apaf-1 expression correlates with advanced melanoma stages, including metastases.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Pathology

Background:

  • Defects in the apoptotic system are implicated in melanoma pathogenesis and chemotherapy resistance.
  • Apoptotic protease-activating factor-1 (Apaf-1) is crucial for apoptosis, working with cytochrome c and caspase-9.
  • Metastatic melanomas frequently exhibit Apaf-1 loss and apoptosis resistance.

Purpose of the Study:

  • To investigate whether Apaf-1 protein is lost during melanoma progression from localized to metastatic stages.
  • To determine the correlation between Apaf-1 expression levels and melanoma pathological stage.

Main Methods:

  • Immunohistochemistry was used to evaluate Apaf-1 protein expression.
  • Apaf-1 expression was assessed in various melanoma lesions: nevi, melanomas in situ, primary melanomas, and metastases.

Main Results:

  • A significant decrease in Apaf-1 expression was observed when comparing nevi and melanomas (P < 0.0001).
  • Primary melanomas with greater tumor thickness showed reduced Apaf-1 expression (P < 0.003).
  • Apaf-1 expression was undetectable in metastatic melanoma lesions.

Conclusions:

  • There is an inverse correlation between Apaf-1 expression and the pathological stage of melanoma.
  • Decreased Apaf-1 expression during melanoma progression likely contributes to increased chemotherapy resistance.

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