Carcinogenesis Advance Access published online on May 19, 2005
Carcinogenesis, doi:10.1093/carcin/bgi131
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR 72202; Department of Physiology & Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72202
* To whom correspondence should be addressed. The isoflavone genistein (GEN), a biologically active component of soy foods, is associated with reduced breast cancer risk in women who consume soy-rich diets. GEN has been reported to influence many biological processes, of which suppression of cell proliferation and stimulation of apoptosis are considered to be major pathways underlying its inhibition of tumorigenesis. This study evaluated the mechanism by which diets containing GEN promote mammary epithelial cell death. We report that mammary glands of young adult female rats exposed from gestation day 4 to postnatal day 50, to AIN-93G diets containing as sole protein source, casein (CAS) supplemented with GEN, or soy protein isolate (SPI+) had increased apoptosis, relative to rats fed CAS diet devoid of GEN. Mammary gland proliferation was unaffected by diet. The increased apoptotic index in mammary glands of GEN and SPI+ rats was accompanied by increased levels of the tumor suppressor protein PTEN, albeit enhanced mammary expression of the pro-apoptotic p21, Bax, and Bok genes was observed only in GEN-fed rats. GEN induced apoptosis in MCF-7 cells concomitant with increased PTEN expression, and this was abrogated by PTEN siRNA. MCF-7 cells treated with serum from GEN- or SPI+-fed rats had increased apoptosis as well as increased levels of the PTEN transcript. PTEN siRNA attenuated the increased apoptotic response of MCF-7 cells to serum from rats fed SPI+ or GEN, although the inhibition to basal (CAS serum) apoptotic levels was achieved only for cells treated with GEN serum. Decreased p21 and Bok gene expression accompanied the inhibition of apoptosis by PTEN siRNA. Data implicate PTEN in the induction of apoptosis by GEN and suggest that the promotion of apoptosis leading to inhibition of tumorigenesis in vivo by diets containing GEN may also involve the distinct activities of yet unknown GEN metabolite(s) and/or other systemic factors induced by GEN.
Received February 20, 2005
Revised April 11, 2005
Accepted May 13, 2005
CARCINOGENESIS
The soy isoflavone genistein promotes apoptosis in mammary epithelial cells by inducing the tumor suppressor PTEN
2 Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR 72202
3 Department of Physiology & Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72202
Rosalia C. M. Simmen, E-mail: simmenrosalia{at}uams.edu
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  T. M. Badger, M. J. J. Ronis, G. Wolff, S. Stanley, M. Ferguson, K. Shankar, P. Simpson, and C.-H. Jo Soy Protein Isolate Reduces Hepatosteatosis in Yellow Avy/a Mice Without Altering Coat Color Phenotype Experimental Biology and Medicine, October 1, 2008; 233(10): 1242 - 1254. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Xiao, Y. Su, R. C. M. Simmen, and F. A. Simmen Dietary soy protein inhibits DNA damage and cell survival of colon epithelial cells through attenuated expression of fatty acid synthase Am J Physiol Gastrointest Liver Physiol, April 1, 2008; 294(4): G868 - G876. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Tamguney and D. Stokoe New insights into PTEN J. Cell Sci., December 1, 2007; 120(23): 4071 - 4079. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Su, F. A. Simmen, R. Xiao, and R. C. M. Simmen Expression profiling of rat mammary epithelial cells reveals candidate signaling pathways in dietary protection from mammary tumors Physiol Genomics, June 19, 2007; 30(1): 8 - 16. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Su, R. R. Eason, Y. Geng, S. Till, T. M. Badger, and R. C.M. Simmen In utero exposure to maternal diets containing soy protein isolate, but not genistein alone, protects young adult rat offspring from NMU-induced mammary tumorigenesis Carcinogenesis, May 1, 2007; 28(5): 1046 - 1051. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Cooper, J. R. Latendresse, D. R. Doerge, N. C. Twaddle, X. Fu, and K. B. Delclos Dietary Modulation of p-Nonylphenol-Induced Polycystic Kidneys in Male Sprague-Dawley Rats Toxicol. Sci., June 1, 2006; 91(2): 631 - 642. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Dave, R. R. Eason, Y. Geng, Y. Su, T. M. Badger, and R. C. M. Simmen Tp53-Associated Growth Arrest and DNA Damage Repair Gene Expression Is Attenuated in Mammary Epithelial Cells of Rats Fed Whey Proteins J. Nutr., May 1, 2006; 136(5): 1156 - 1160. [Abstract] [Full Text] [PDF]
|
|