Chen, ZhihongGe, YinlinLandman, NatalieKang, Jing2011-02-212002Chen, Zhihong, Yinlin Ge, Natalie Landman, and Jing X Kang. 2002. Decreased expression of the mannose 6- phosphate/insulin-like growth factor-II receptor promotes growth of human breast cancer cells. BMC Cancer 2: 18.1471-2407http://nrs.harvard.edu/urn-3:HUL.InstRepos:4728727Background: Loss or mutation of the mannose 6-phosphate/insulin-like growth factor-II receptor (M6P/IGF2R) has been found in breast cancer. However, whether or not decreased levels of functional M6P/IGF2R directly contribute to the process of carcinogenesis needs to be further verified by functional studies. Methods: In this study, using viral and ribozyme strategies we reduced the expression of M6P/IGF2R in human breast cancer cells and then examined the effect on growth and apoptosis of these cells. Results: Our results showed that infection of MCF-7 cells with the adenovirus carrying a ribozyme targeted against the M6P/IGF2R mRNA dramatically reduced the level of transcripts and the functional activity of M6P/IGF2R in these cells. Accordingly, cells treated with the ribozyme exhibited a higher growth rate and a lower apoptotic index than control cells (infected with a control vector). Furthermore, decreased expression of M6P/IGF2R enhanced IGF-II-induced proliferation and reduced cell susceptibility to TNF-induced apoptosis. Conclusions: These results suggest that M6P/IGF2R functions as a growth suppressor and its loss or mutation may contribute to development and progression of cancer. This study also demonstrates that adenoviral delivery of the ribozyme provides a useful tool for investigating the role of M6P/IGF2R in regulation of cell growth.en-UStumor-necrosis-factor6-Phosphate Receptorfactor-alphafactor-betasuppressor genegrowth-factor-2 receptorhepatocellular-carcinomaM6P/IGF2 receptorcathepsin-DcarcinogenesisJournal Article2011-02-2110.1186/1471-2407-2-18