| First Author | Akaboshi S | Year | 2009 |
| Journal | Am J Pathol | Volume | 175 |
| Issue | 4 | Pages | 1675-85 |
| PubMed ID | 19729480 | Mgi Jnum | J:153058 |
| Mgi Id | MGI:4360815 | Doi | 10.2353/ajpath.2009.090069 |
| Citation | Akaboshi S, et al. (2009) HMGA1 is induced by Wnt/beta-catenin pathway and maintains cell proliferation in gastric cancer. Am J Pathol 175(4):1675-85 |
| abstractText | The development of stomach cancer is closely associated with chronic inflammation, and the Wnt/beta-catenin signaling pathway is activated in most cases of this cancer. High-mobility group A (HMGA) proteins are oncogenic chromatin factors that are primarily expressed not only in undifferentiated tissues but also in various tumors. Here we report that HMGA1 is induced by the Wnt/beta-catenin pathway and maintains proliferation of gastric cancer cells. Specific knockdown of HMGA1 resulted in marked reduction of cell growth. The loss of beta-catenin or its downstream c-myc decreased HMGA1 expression, whereas Wnt3a treatment increased HMGA1 and c-myc transcripts. Furthermore, Wnt3a-induced expression of HMGA1 was inhibited by c-myc knockdown, suggesting that HMGA1 is a downstream target of the Wnt/beta-catenin pathway. Enhanced expression of HMGA1 coexisted with the nuclear accumulation of beta-catenin in about 30% of gastric cancer tissues. To visualize the expression of HMGA1 in vivo, transgenic mice expressing endogenous HMGA1 fused to enhanced green fluorescent protein were generated and then crossed with K19-Wnt1/C2mE mice, which develop gastric tumors through activation of both the Wnt and prostaglandin E2 pathways. Expression of HMGA1-enhanced green fluorescent protein was normally detected in the forestomach, along the upper border of the glandular stomach, but its expression was also up-regulated in cancerous glandular stomach. These data suggest that HMGA1 is involved in proliferation and gastric tumor formation via the Wnt/beta-catenin pathway. |
