期刊
BRITISH JOURNAL OF CANCER
卷 114, 期 11, 页码 1251-1260出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2016.112
关键词
LGR5; splice variants; Ki-67; colorectal cancer; cell cycle; antitumour drug resistance
类别
资金
- MEXT KAKENHI [24689054]
- Grants-in-Aid for Scientific Research [24689054] Funding Source: KAKEN
Background: Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a target of Wnt signalling and considered both a cancer stem cell marker and intestinal stem cell marker. We found first some splice variants of LGR5 in human intestine and elucidated the functional feature of full-length LGR5 (LGR5FL). Methods: Reverse transcript PCR using mRNA extracted from intestine revealed the existence of LGR5 splice variants. We designed an antibody that recognises only LGR5FL and assessed immunohistochemically the distribution of LGR5FL-positive cells and Ki-67-positive cells in clinical samples. Results: Two LGR5 splice variants were expressed in the human intestine crypt cells; one lacked exon 5 and the other lacked exons 5-8. Only LGR5FL appeared during cell cycle arrest, whereas the transcript variants appeared when the cell cycle was proceeding. Immunohistochemistry and in situ hybridisation showed that LGR5FL-positive cells were negative for Ki-67. Comparing prechemotherapy and post-chemotherapy specimens, the population of LGR5FL-positive cells significantly increased with therapy (P<0.01). Conclusions: The function of LGR5FL-positive cells had low cell proliferative ability compared with the cells, which expressed splice variants of LGR5 and remained after chemotherapy. Designing therapeutic strategies that target LGR5FL-positive cells seems to be important in colorectal cancer.
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