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Jing X Kang

Publications and source records attributed to Jing X Kang.

23 records · Page 2Linked to original sources
PubMed2002

Decreased expression of the mannose 6-phosphate/insulin-like growth factor-II receptor promotes growth of human breast cancer cells.

BACKGROUND: 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 a 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.

Adenoviridae↗
PubMed2002

Gene transfer of the Caenorhabditis elegans n-3 fatty acid desaturase inhibits neuronal apoptosis.

Previous studies have shown that n-3 polyunsaturated fatty acids (PUFAs) can exert an antiapoptotic effect on neurons. The present study was designed to investigate whether the Caenorhabditis elegans fat-1 gene encoding an n-3 fatty acid desaturase (an enzyme that converts n-6 PUFAs to corresponding n-3 PUFAs) can be expressed functionally in rat cortical neurons and whether its expression can change the ratio of n-6 : n-3 fatty acids in the cell membrane and exert an effect on neuronal apoptosis. Infection of primary rat cortical cultures with Ad-fat-1 resulted in high expression of the fat-1 gene. Lipid analysis indicated a decrease in the ratio of n-6 : n-3 PUFAs from 5.9 : 1 in control cells, to 1.45 : 1 in cells expressing the n-3 fatty acid desaturase. Accordingly, the levels of prostaglandin E2, an eicosanoid derived from n-6 PUFA, were significantly lower in cells infected with Ad-fat-1 when compared with control cells. Finally, there was a significant inhibition of growth factor withdrawal-induced apoptotic cell death in neurons expressing the fat-1 gene. These results demonstrate that expression of the fat-1 gene can inhibit apoptotic cell death in neurons and suggest that the change in the n-6 : n-3 fatty acid ratio may play a key role in this protective effect.

Animals↗
PubMed2002

Differential expression of the mannose 6-phosphate/ insulin-like growth factor-II receptor in human breast cancer cell lines of different invasive potential.

BACKGROUND: Hypersecretion of the precursor of the lysosomal protease cathepsin D (procathepsin D) has been implicated in the invasive phenotype of human breast cancer. However, the mechanism of the abnormal secretion of procathepsin D remains unclear. Since the mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) plays a central role in the intracellular transport and endocytosis of M6P-containing lysosomal enzymes, a deficiency in functional M6P/IGF2R may underlie the hypersecretion of procathepsin D in invasive tumors. MATERIAL/METHODS: In the present study, we compared the profiles of cathepsin D and the M6P/IGF2R between the highly invasive MDA-MB-231 and the non-invasive MCF-7 cell lines. RESULTS: MDA-MB-231cells were confirmed to secrete a much larger proportion of procathepsin D into the medium than MCF-7 cells. Addition of M6P to the culture medium significantly altered the secretion of procathepsin D by MCF-7 cells, but had little effect on cathepsin D distribution in MDA-MB-231cells. Both the M6P-binding capacity and the endocytosis of exogenous M6P-bearing proteins in MDA-MB-231 cells were far less than those in MCF-7 cells. mRNA analysis indicated that the levels of the M6P/IGF2R mRNA in MDA-MB-231 cells were not lower but were even higher than that in MCF-7 cells. Sequence analysis indicated a difference in the 3'-untranslated region of M6P/IGF2R between the two cell lines, but no mutation in the M6P-binding domain of the receptor. CONCLUSIONS: The results suggest that a potential defect in a post-transcriptional process (e.g., translation) may exist during synthesis of the M6P/IGF2R in MDA-MB-231cells, leading to failure to express sufficient functional M6P/IGF2R and thereby resulting in the hypersecretion of procathepsin D.

3' Untranslated Regions↗
PubMedDate not supplied

Effects of adenoviral gene transfer of C. elegans n-3 fatty acid desaturase on the lipid profile and growth of human breast cancer cells.

BACKGROUND: Current evidence from both experimental and human studies indicates that omega-6 polyunsaturated fatty acids (n-6 PUFAs) promote breast tumor development, whereas long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) exert suppressive effects. The ratio of n-6 to n-3 fatty acids appears to be an important factor in controlling tumor development. Human cells usually have a very high n-6/n-3 fatty acid ratio because they cannot convert n-6 PUFAs to n-3 PUFAs due to lack of an n-3 desaturase found in C. elegans. MATERIALS AND METHODS: Adenoviral strategies were used to introduce the C. elegans fat-1 gene encoding an n-3 fatty acid desaturase into human breast cancer cells followed by examination of the n-6/n-3 fatty acid ratio and growth of the cells. RESULTS: Infection of MCF-7 cells with an adenovirus carrying the fat-1 gene resulted in a high expression of the n-3 fatty acid desaturase. Lipid analysis indicated a remarkable increase in the levels of n-3 PUFAs accompanied with a large decrease in the contents of n-6 PUFAs, leading to a change of the n-6/n-3 ratio from 12.0 to 0.8. Accordingly, production of the eicosanoids derived from n-6 PUFA was reduced significantly in cells expressing the fat-1 gene. Importantly, the gene transfer induced mass cell death and inhibited cell proliferation. CONCLUSION: The gene transfer of the n-3 fatty acid desaturase, as a novel approach, can effectively modify the n-6/n-3 fatty acid ratio of human tumor cells and provide an anticancer effect, without the need of exogenous n-3 PUFA supplementation. These data also increase the understanding of the effects of n-3 fatty acids and the n-6/n-3 ratio on cancer prevention and treatment.

Adenoviridae↗