The spot 14 protein inhibits growth and induces differentiation and cell death of human MCF-7 breast cancer cells.
The S14 (spot 14) gene encodes a protein that is predominantly expressed in lipogenic tissues, such as the liver, white and brown adipose tissues and the lactating mammary glands. Accumulated evidence suggests that S14 could play an important role in the induction of lipogenic enzymes. In humans, the S14 locus resides in the chromosome region 11q13, which is frequently amplified in breast tumours, and as a result, it has been suggested that this protein could play a role in the metabolism and growth of these kinds of tumours. In the present study, we have examined the effects of S14 overexpression in MCF-7 human breast cancer cells. We found that S14 causes (i) an inhibition of cell proliferation and of anchorage-independent growth, (ii) a marked reduction in the number of viable cells and (iii) the induction of differentiation and cell death of these cells. The inhibition of cell growth was associated with a decrease in the expression of cyclin D1 and a reduction of cyclin D1 promoter activity. Increased expression of S14 also caused the accumulation of cytochrome c in the cytosol and loss of mitochondrial membrane potential. These findings suggest that S14 may function as an important modulator of tumorigenesis in human breast by decreasing cell growth and inducing cell death and differentiation.
Sanchez-Rodriguez
Jinny
J
Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain.
Kaninda-Tshilumbu
John P
JP
Santos
Angel
A
Perez-Castillo
Ana
A
D001943:Breast Neoplasms / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002762:Cholecalciferol / Q000494:pharmacology; D019938:Cyclin D1; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors; D014212:Tretinoin / Q000494:pharmacology
C477819:15-deoxyprostaglandin J2; D009687:Nuclear Proteins; D011506:Proteins; C051065:THRSP protein, human; D014157:Transcription Factors; D019938:Cyclin D1; D002762:Cholecalciferol; D014212:Tretinoin; D015230:Prostaglandin D2