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

被引:32
作者
Kiiveri, S
Liu, JQ
Arola, J
Heikkilä, P
Kuulasmaa, T
Lehtonen, E
Voutilainen, R
Heikinheimo, M [1 ]
机构
[1] Univ Helsinki, Childrens Hosp, Biomedicum, FIN-00014 Helsinki, Finland
[2] Univ Helsinki, Program Dev & Reprod Biol, Biomedicum, FIN-00014 Helsinki, Finland
[3] Univ Helsinki, Dept Pathol, FIN-00014 Helsinki, Finland
[4] Univ Helsinki, Cent Hosp, Dept Pathol, FIN-00290 Helsinki, Finland
[5] Kuopio Univ Hosp, Dept Pediat, SF-70210 Kuopio, Finland
基金
芬兰科学院;
关键词
adrenal gland; adrenocortical tumor; GATA-6; SF-1; transcription factor;
D O I
10.1016/j.mce.2005.01.012
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:47 / 56
页数:10
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