Submitted to: Toxicological Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 1, 2002
Publication Date: September 15, 2002
Citation: ROWLANDS, J.C., HAKKAK, R., RONIS, M., BADGER, T.M. ALTERED MAMMARY GLAND DIFFERENTIATION AND PROGESTERONE RECEPTOR EXPRESSION IN RATS FED SOY AND WHEY PROTEINS. TOXICOLOGICAL SCIENCES. 2002. v. 70. p. 40-46. Interpretive Summary: The normal development and function of the mammary gland is dependent upon steroid hormones produced in the ovary that travel to the mammary gland and bind to protein receptors. The combination of these steroid hormones (estrogen and progesterone) and the protein receptors (ER-alpha, ER-beta and PR) turn on some genes and turn-off others. Thus, the levels of these receptors are important to the development and function of the mammary gland. One possible mechanism by which dietary factors could prevent mammary gland cancers is to alter the levels of these receptors. We studies this and found that diets made with soy protein isolate and whey protein hydrolysate may change the profile of these steroid receptor proteins and this could be linked to the mechanism of breast cancer prevention. Further studies are underway to learn more about the process, especially in infant animals.
Technical Abstract: There are suspected links between an animal's diet, differientiation status of a target tissue, and sensitivity to chemically induced cancer. We have demonstrated that rats fed AIN93G diets made with soy protein isolate (SPI) or whey protein hydrolsate (WPH) had lower incidence of 7,12-dimethylbenz(a)anthracene (DMBA)-induced adenocarcinoma than rats fed the same diet made with casein (CAS). The current study was conducted to determine the differentiation status of teh mammary glands druing development. Ofspring of rats (n-10/group) were fed diets made with SPI, WPH, or CAS throughout life (beginning on gestation day 4) and were sacrificed on postnatal day (PND) 21, PND 33, PND 50 or on metaestrous between PND 48 and PND 51. There were no significant differences between the numbers of mammary terminal end buds (TEBs) or lobuloalveoli (LOB) between any of teh diet groups at PND 21 or PND 33, but at PND 50 there was an 75% decrease in the mean numbers of TEBs/mm2 in the SPI- or WPH-fed rats, compated with the CAS-fed rats (p = 0.09 and p = 0.06, respectively). In rats sacrificed in metaestrous, there were no significant differences in the proliferation indes (PI) in the TEBs or LOB between any of the diet groups. In metaestrous rats, there were twice as many cells expressing estrogen receptor beta (ERbata; ~60%) compared with estrogen receptor alpha (ERalpha; ~30%) in the LOB and 1.5 times more ERbeta (~60%) compared with estrogen receptor alpha (ERalpha, ~40%) in the TEBs. There were no diet-dependent differences in expression of ERalpha or ERbeta. Similarly, there were no differences between the diet groups in progesterone receptor (PR) expressing LOB cells. However, in the TEBs there was a diet-dependent difference in PR positive cells with a 34% increase (p<0.05) in the SPI-fed rats and a 38% increase (p<0.05) in the WPH-fed rats compared with the CAS-fed rats. Theseresults show that the type if dietary protein alters the phenotype of mammary epithelia in the TEBs. THe SPI- and WPH-dependent changes in mammary differentiation may contribute to the reduced sensitivity to DMBA-induced mammary cancer in rats fed these proteins.