Estrogen prevents sustained COLO-205 human colon cancer cell growth by inducing apoptosis, decreasing c-myb protein, and decreasing transcription of the anti-apoptotic protein bcl-2.
The proto-oncogene c-myb is overexpressed in human colon cancer cells. c-myb is known to be affected by estrogen in some breast cancers and leukemias. However, the mechanism of c-myb regulation via estrogen in colon cancer requires further investigation. Human COLO-205 colon cancer cells were cultured and treated with beta-estradiol for 24 h. Apoptosis was quantified using acridine orange/propidium iodide labeling and confirmed with DNA fragmentation gel electrophoresis. Expression of c-myb protein was assessed via SDS-PAGE and immunoblotting and RT-PCR was used to quantify bcl-2 RNA. Protein and RNA expression levels were also assayed after c-myb siRNA treatment for 24 h. We demonstrate an increase in apoptosis after 24 h of beta-estradiol treatment of human COLO-205 colon cancer cells. Estrogen treatment also decreases c-myb protein levels as well as expression of its transcriptional target bcl-2. Suppression of c-myb protein also results in increased apoptosis and decreases bcl-2 expression. These results indicate that estrogen has a protective effect from sustained colon cancer cell growth at least partly through suppression of c-myb and bcl-2.
Wilkins
Heather R
HR
Department of Natural Sciences, Assumption College, 500 Salisbury Street, Worcester, MA 01609, USA. hwilkins@assumption.edu
Doucet
Kristin
K
Duke
Victoria
V
Morra
Amber
A
Johnson
Nicole
N
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D020598:Proto-Oncogene Proteins c-myb / Q000032:analysis*; D034741:RNA, Small Interfering / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis; D014158:Transcription, Genetic / Q000187:drug effects*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2; D020598:Proto-Oncogene Proteins c-myb; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen; D004958:Estradiol