ICER-IIγ is a tumor suppressor that mediates the antiproliferative activity of cAMP

• Published in: Oncogene Vol. 17; no. 23; pp. 3015 - 3019
• Main Authors: RAZAVI, R, RAMOS, J. C, YEHIA, G, SCHLOTTER, F, MOLINA, C. A
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 10.12.1998; Nature Publishing Group
• Subjects: Biological and medical sciences; Brain tumors; Cell cycle; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Choriocarcinoma; Cyclic AMP; Cyclic AMP response element modulator; DNA biosynthesis; Fundamental and applied biological sciences. Psychology; Molecular and cellular biology; Pituitary; Regulatory sequences; Transcription factors; Tumor cells; Tumor suppressor genes; Human; Cell proliferation; Rodentia; Cyclic AMP; Carcinogenesis; Vertebrata; Regulation(control); Mammalia; Cell line; Mouse; Cell cycle; Tumor; Transcription factor; Tumor suppressor gene
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1202225

The second messenger cAMP inhibits the proliferation of most cell types. The nuclear response of cAMP is mediated by transcription factors like the cAMP-Responsive Element Modulator (CREM) gene. One of the products of the CREM gene, the transcriptional repressor Inducible cAMP Early Repressor-IIγ (ICER-IIγ), is induced by cAMP. ICER-IIγ blocks cells at the G2/M boundary of the cell cycle. Here we show that ICER-IIγ dramatically inhibits the growth and DNA synthesis of mouse pituitary tumor cells and human choriocarcinoma cells. This alteration in cell growth is coupled with reduced ability of these cells to grow in an anchorage-independent manner and to form tumors in mice. These data demonstrate that ICER-IIγ is a tumor suppressor gene product mediating the antiproliferative activity of cAMP.