Decreased expression of Apaf-1 with progression of melanoma

Rita Mustika, Arief Budiyanto, Chikako Nishigori, Masamitsu Ichihashi, Masato Ueda

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

Defects in apoptotic system may contribute in the pathogenesis and resistance of malignant melanoma cells to chemotherapy. Apoptotic protease-activating factor-1 (Apaf-1) is a cell death effector that acts with cytochrome c and caspase-9 to mediate apoptosis. Recently it was shown that metastatic melanomas often lose Apaf-1 and are concomitantly resistant to apoptosis. It is not known, however, whether Apaf-1 protein is lost during melanoma progression from localized to metastatic tumor. To this end, we evaluated Apaf-1 protein expression by immunohistochemistry in 10 cases of human nevi, 11 melanomas in situ, 26 primary melanomas and 15 metastases. Significant decreases in Apaf-1 expression was observed when comparing nevi and melanomas (chi-square = 33.719; P < 0.0001). Moreover, primary melanomas with greater tumor thickness showed lesser expression of Apaf-1 (chi-square = 16.182; P < 0.003). Intriguingly, we were unable to detect Apaf-1 expression in lesions of metastatic melanomas. These data demonstrated that there is an inverse correlation between Apaf-1 expression and pathologic stage of melanoma. This suggests that the decreased expression of Apaf-1 seen in correlation with melanoma progression renders melanoma more resistant to chemotherapy.

Original languageEnglish
Pages (from-to)59-62
Number of pages4
JournalPigment Cell Research
Volume18
Issue number1
DOIs
Publication statusPublished - 1 Feb 2005

Keywords

  • Apoptotic protease-activating factor-1
  • Chemoresistancy
  • Immunohistochemistry
  • Melanoma
  • Nevus
  • Protein expression
  • Tumor progression

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