9988

DMTF1

DMP1|DMTF|MRUL|hDMP1;cyclin D binding myb-like transcription factor 1;DMTF1;cyclin D binding myb-like transcription factor 1

cyclin D-binding Myb-like protein|cyclin-D-binding Myb-like transcription factor 1|cyclin-D-interacting Myb-like protein 1|hDMTF1

7q21

protein-coding

Dmp1 (Dmtf1) is activated by oncogenic Ras-Raf signaling and induces cell-cycle arrest in an Arf, p53-dependent fashion. The survival of K-ras(LA) mice was shortened by approximately 15 weeks in both Dmp1(+/-) and Dmp1(-/-) backgrounds, the lung tumors of which showed significantly decreased frequency of p53 mutations compared to Dmp1(+/+). Approximately 40% of K-ras(LA) lung tumors from Dmp1(+/+) mice lost one allele of the Dmp1 gene, suggesting the primary involvement of Dmp1 in K-ras-induced tumorigenesis. Loss of heterozygosity (LOH) of the hDMP1 gene was detectable in approximately 35% of human lung carcinomas, which was found in mutually exclusive fashion with LOH of INK4a/ARF or that of P53. Thus, DMP1 is a pivotal tumor suppressor for both human and murine lung cancers.

ECRG-1 (esophageal cancer-related gene 1) has been previously found to be down-regulated in human esophagus cancer. Transient expression of green fluorescent protein (GFP)-tagged ECRG1 showed plasma membrane localization. Treatment of esophagus cancer cell line (NEC) with ECRG-1 fusion protein and over-expression of ECRG-1 in NEC cells can significantly reduce the in vitro proliferation rate of NEC cells. Treatment of established NEC tumors in the nude mice with ECRG-1 fusion protein leads to decreased tumor weight and volume. Over-expression of ECRG-1 in NEC cells can also inhibit tumor formation in nude mice. Cell-cycle analysis showed that over-expression of ECRG-1 in NEC cells results in G(2)/M phase arrest. Our findings indicate that ECRG1 may be a candidate tumor suppressor gene for esophageal cancer (EC) involved in cell-cycle control. Since ECRG-1 gene significantly suppresses the growth of NEC cells both in vitro and in vivo, its loss may contribute to the causation and progression of the EC in Lin-xian county, which is a high incidence area of EC in China.