Transcriptional suppression of synuclein gamma (SNCG) expression in human breast cancer cells by the growth inhibitory cytokine oncostatin M.
Previously, we have shown that synuclein gamma (SNCG), a member of the brain protein synuclein family, is highly expressed in human infiltrating breast carcinomas but not expressed in normal or benign breast tissues. The SNCG mRNA was also detected in several human breast cancer cell lines with the highest expression found in H3922, a cell line derived from an infiltrating ductal carcinoma. In this study, we show that expression of SNCG mRNA in H3922 cells is significantly decreased by treating cells with the cytokine oncostatin M (OM) who has a growth-inhibitory effect on these cells. A decrease in SNCG mRNA level can be detected as early as 30 min after OM addition. By 4 h OM treatment, the level of SNCG mRNA was decreased to 70% of control, and by 24 h the mRNA was below detectable level. Western blot analysis further demonstrated the suppression of SNCG protein expression by OM. The level of SNCG protein in H3922 cells was reduced more than 90% by OM after 2 days. Since OM-induced growth inhibition occurs after 3-4 days, the down-regulation of SNCG expression appears to proceed the effect of OM on cell growth. Additional experiments to measure the transcriptional rates of SNCG indicate that the observed OM-induced down-regulation of SNCG mRNA occurs mainly at the transcriptional level. In an attempt to examine the role of SNCG gene in the proliferation of breast cancer cells, SNCG cDNA was stably transfected into MCF-7 cells that do not express endogenous SNCG gene. Examination of cell growth under anchorage-dependent and anchorage-independent conditions demonstrates that over expression of SNCG gene significantly stimulated the growth of MCF-7 cells both in monolayer culture and in soft agar. These data together suggest that SNCG may play a role in cell proliferation.
Liu
J
J
VA Palo Alto Health Care System, CA 94304, USA. liu@icon.palo-alto.med.va.gov
Spence
M J
MJ
Zhang
Y L
YL
Jiang
Y
Y
Liu
Y E
YE
Shi
Y E
YE
D015152:Blotting, Northern; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051843:Synucleins; D014407:Tumor Cells, Cultured / Q000187:drug effects
D006131:Growth Inhibitors; D009419:Nerve Tissue Proteins; C508351:OSM protein, human; D010455:Peptides; D012333:RNA, Messenger; D051843:Synucleins; D053683:Oncostatin M