Expression of Wnt and TGF-β pathway components and key adrenal transcription factors in adrenocortical tumors: Association to carcinoma aggressiveness

Helka Parviainen, Anja Schrade, Sanne Kiiveri, Renata Prunskaite-Hyyryläinen, Caj Haglund, Seppo Vainio, David B. Wilson, Johanna Arola, Markku Heikinheimo

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Factors controlling benign and malignant adrenocortical tumorigenesis are largely unknown, but several mouse models suggest an important role for inhibin-alpha (INHA). To show that findings in the mouse are relevant to human tumors and clinical outcome, we investigated the expression of signaling proteins and transcription factors involved in the regulation of INHA in human tumor samples. {dot operator} Thirty-one adrenocortical tumor samples, including 13 adrenocortical carcinomas (ACCs), were categorized according to Weiss score, hormonal profile, and patient survival data and analyzed using immunohistochemistry and RT-PCR.Expression of the TGF-β signaling mediator SMAD3 varied inversely with Weiss score, so that SMAD3 expression was lowest in the most malignant tumors. By contrast, SMAD2 expression was upregulated in most malignant tumors. Wnt pathway co-receptors LRP5 and LRP6 were predominantly expressed in benign adrenocortical tumors. In ACCs, expression of transcription factors GATA-6 and SF-1 correlated with that of their target gene INHA. Moreover, the diminished expression of GATA-6 and SF-1 in ACCs correlated with poor outcome.We conclude that the factors driving INHA expression are reduced in ACCs with poor outcome, implicating a role for INHA as a tumor suppressor in humans.

Original languageEnglish
Pages (from-to)503-509
Number of pages7
JournalPathology Research and Practice
Volume209
Issue number8
DOIs
StatePublished - Aug 2013

Keywords

  • Adenoma
  • Carcinoma
  • Inhibin
  • Signaling pathway
  • Transcription factor

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