Transcription factors GATA-6, SF-1, and cell proliferation in human adrenocortical tumors

Mol Cell Endocrinol. 2005 Apr 15;233(1-2):47-56. doi: 10.1016/j.mce.2005.01.012.

Abstract

Transcription factor GATA-6 is expressed in fetal and adult human adrenal cortex and has been suggested to have a role in adrenal androgen synthesis. In other tissues GATA-6 has been linked to the cell cycle regulation and the dedifferentiation of carcinoma cells. GATA-6 has been shown to be downregulated in mouse adrenocortical tumors, but has not been studied in human adrenocortical tumors in detail. We have now analyzed GATA-6 expression in 20 human adrenocortical adenomas and 16 carcinomas using Northern blot analysis and immunohistochemistry. GATA-6 mRNA and protein expression was remarkably diminished in adrenocortical carcinomas as compared to normal adrenal cortex and adenomas (p<0.05). In opposite to other tumor types GATA-6 expression was, however, high in virilizing carcinomas. Steroidogenic factor 1 (SF-1) has been functionally linked to GATA-6, and the expression of these two factors correlated in the adrenal tumors. Furthermore, GATA-6 immunoreactivity was linked to P450c17 expression. In contrast to GATA-6, we found upregulated cyclin-dependent kinase inhibitor p21 and proliferation marker Ki67 in adrenocortical carcinomas indicating that GATA-6 is not linked to cell proliferation in human adrenal tumors. Taken together, the present and earlier results link GATA-6 to adrenocortical steroidogenesis and to the benign adrenocortical phenotype.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Neoplasms / genetics
  • Adrenal Cortex Neoplasms / metabolism*
  • Adrenal Glands / chemistry
  • Adrenal Glands / cytology
  • Adrenocortical Adenoma / genetics
  • Adrenocortical Adenoma / metabolism*
  • Adrenocortical Carcinoma / genetics
  • Adrenocortical Carcinoma / metabolism*
  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Proliferation
  • Child
  • Child, Preschool
  • Cyclin-Dependent Kinase Inhibitor p21
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Female
  • GATA6 Transcription Factor
  • Homeodomain Proteins
  • Humans
  • Infant
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism
  • Male
  • Middle Aged
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Receptors, Cytoplasmic and Nuclear
  • Steroidogenic Factor 1
  • Transcription Factors / analysis
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • CDKN1A protein, human
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • DNA-Binding Proteins
  • GATA6 Transcription Factor
  • GATA6 protein, human
  • Homeodomain Proteins
  • Ki-67 Antigen
  • NR5A1 protein, human
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Steroidogenic Factor 1
  • Transcription Factors
  • steroidogenic factor 1, mouse