Growth factor signaling enhances aromatase activity of breast cancer cells via post-transcriptional mechanisms.
It has been demonstrated that growth factors produced by breast cancer cells stimulate aromatase expression in both breast cancer and adjacent adipose fibroblasts and stromal cells. However, whether these growth factors affect aromatase activity by other mechanisms still remain unclear. In the current study, MCF-7aro and T47Daro aromatase transfected breast carcinoma cells were used to explore the mechanisms of post-transcriptional regulation of aromatase activity by growth factor pathways. Our study reveals that PI3K/Akt and MAPK inhibitors suppressed aromatase activity in MCF-7aro cells. However, PI3K/Akt pathway inhibitors stimulated aromatase activity in T47Daro cells. This is due to enhanced MAPK phosphorylation as compensation after the PI3K/Akt pathway has been blocked. IGF-1 treatment increased aromatase activity in both breast cancer cell lines. In addition, LTEDaro cells (long-term estrogen deprived MCF-7aro cells) which have enhanced MAPK activity, show higher aromatase activity compared to parental MCF-7aro cells, but the aromatase protein level remains the same. These results suggest that aromatase activity could be enhanced by growth factor signaling pathways via post-transcriptional mechanisms.
Department of Chemistry, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH 44115, USA. B.su@csuohio.edu
Bin
B
Su
Cynthie
C
Wong
Yanyan
Y
Hong
Shiuan
S
Chen
D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000494:pharmacology; D001943:Breast Neoplasms / Q000201:enzymology* / Q000378:metabolism; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured
D001141:Aromatase; D047072:Aromatase Inhibitors; D007334:Insulin-Like Growth Factor I; D036341:Intercellular Signaling Peptides and Proteins; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases