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

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.

• Authors: Sanne Kiiveri, Jianqi Liu, Johanna Arola, Päivi Heikkilä, Tiina Kuulasmaa, Eero Lehtonen, Raimo Voutilainen, Markku Heikinheimo
• Journal: Molecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 233 Issue 1-2 Pg. 47-56 (Apr 15 2005) ISSN: 0303-7207 [Print] Ireland
• PMID: 15767045 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

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