Induction of Dlk1 by PTTG1 Inhibits Adipocyte Differentiation and Correlates with Malignant Transformation

被引:24
作者
Espina, Agueda G. [1 ]
Mendez-Vidal, Cristina [1 ]
Moreno-Mateos, Miguel A. [1 ]
Saez, Carmen [2 ]
Romero-Franco, Ana [1 ]
Japon, Miguel A. [2 ]
Pintor-Toro, Jose A. [1 ]
机构
[1] CABIMER CSIC, Ctr Andaluz Biol Mol & Med Regenerat, Seville 41092, Spain
[2] Hosp Univ Virgen Rocio, Dept Anat Patol, Seville 41013, Spain
关键词
PITUITARY-ADENOMAS; MESSENGER-RNA; HUMAN HOMOLOG; HUMAN SECURIN; GENE PTTG; EXPRESSION; CANCER; PROTEIN; PREF-1; IDENTIFICATION;
D O I
10.1091/mbc.E08-09-0965
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Pituitary tumor-transforming gene-1 (PTTG1) is an oncogene highly expressed in a variety of endocrine, as well as nonendocrine-related cancers. Several tumorigenic mechanisms for PTTG1 have been proposed, one of the best characterized being its capacity to act as a transcriptional activator. To identify novel downstream target genes, we have established cell lines with inducible expression of PTTG1 and a differential display approach to analyze gene expression changes after PTTG1 induction. We identified dlk1 (also known as pref-1) as one of the most abundantly expressed PTTG1 targets. Dlk1 is known to participate in several differentiation processes, including adipogenesis, adrenal gland development, and wound healing. Dlk1 is also highly expressed in neuroendocrine tumors. Here, we show that PTTG1 overexpression inhibits adipogenesis in 3T3-L1 cells and that this effect is accomplished by promoting the stability and accumulation of Dlk1 mRNA, supporting a role for PTTG1 in posttranscriptional regulation. Moreover, both pttg1 and dlk1 genes show concomitant expression in fetal liver and placenta, as well as in pituitary adenomas, breast adenocarcinomas, and neuroblastomas, suggesting that PTTG1 and DLK1 are involved in cell differentiation and transformation.
引用
收藏
页码:3353 / 3362
页数:10
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