NASA Scientific and Technical Aerospace Reports

The objective was to produce breast cancer model in female rats, fed casein containing diet, by gavage administration of
DMBA, and to investigate whether the tumor development is controlled by replacement of casein with soybean protein. Two
separate experiments were done. For each experiment, Twenty 21-day old female Sprague Dawley rats were used. They were
divided into 4 groups. Animals from groups 1 and 2 received standard AIN-76A diet containing 20% casein and those of
groups 3 and 4 received same diet containing 20% soybean protein. Animals of groups 2 and 4 received DMBA in sesame
oil by gavage (15 mg per animal). Control animals (groups 1 and 3) received the vehicle. Animals were weighed and palpated
twice weekly. At the end of the study (postinjection time of 122 days), the animals were killed by carbon dioxide asphyxiation.
All tumors were detected by palpation and at autopsy biopsy specimens were taken for histological analysis. Breast tissues
were removed, quickly frozen in liquid nitrogen and stored at -800C for biochemical analysis. Even though multiple tumors
were observed in some animals of both groups, the number of tumors per rat was less in soyprotein group than casein group
at any time point after DMBA exposure. Incidence of tumors was less in soybean protein group than that in casein group.
There was no tumor in any animal which did not receive the carcinogen. Casein group had 20% grade I, 60% grade II and
20% grade III mammary gland adenocarcinoma. However, the soybean group had 100% grade I adenocarcinoma and no
aggressive grade II or III. These findings suggest that the soybean protein may protect against the development of a more
aggressive mammary gland adenocarcinoma. Furthermore, there was a delay in the development of adenocarcinoma in the
soybean group challenged with DMBA in comparison to the animals fed casein and challenged with DMBA.
DTIC
Cancer; Diets; Gene Expression; Mammary Glands; Proteins; Soybeans
20040111760 Minnesota Univ., Minneapolis, MN
Dietary Phytoestrogens and Prostate Cancer Prevention
Kurzer, Mindy S.; May 2004; 6 pp.; In English
Contract(s)/Grant(s): DAMD17-02-1-0101
Report No.(s): AD-A425976; No Copyright; Avail: CASI; A02, Hardcopy
The main objective of this project is to evaluate the effects of soy phytoestrogen consumption on reproductive hormones
and prostate tissue markers of cell proliferation and androgen action in men at high risk of prostate cancer. The hypothesis
is that alteration of endogenous hormones is a mechanism by which soy phytoestrogens prevent prostate cancer. A randomized
parallel arm study will be performed, in which 90 men at high risk of prostate cancer will be randomized to receive one of
three dietary supplements for six months: I) soy powder containing phytoestrogens; 2) phytoestrogen-free soy powder; or 3)
phytoestrogen-free milk powder. Urine and blood will be collected at 0, 3 and 6 months, for evaluation of prostate cancer risk
factors, including serum hormones (testosterone, dihydrotestosterone, androstenedione, dehydroepiandrosterone, estradiol,
estrone, 3alpha, 17beta- androstanediol glucuronide, sex hormone binding globulin) and prostate specific antigen, as well as
urinary estrogen and phytoestrogen metabolites. Before and after the intervention, prostate biopsy will be performed to
evaluate prostate tissue expression of apoptosis (TUNEL assay, Bax, Bcl-2), proliferation (Ki67, PCNA and androgen receptor
density. At this point, 10 subjects have completed the feeding study, 17 subjects are enrolled, and biological samples have been
collected, processed and stored.
DTIC
Cancer; Diets; Prevention; Prostate Gland
20040111969 Saint Luke’s Hospital Center, New York, NY, USA
Autocine and Paracrine Control of Breast Cancer Growth by Sex Hormone-Binding Globulin
Rosner, William; Apr. 2004; 16 pp.; In English
Contract(s)/Grant(s): DAMD17-02-1-0572
Report No.(s): AD-A425713; No Copyright; Avail: CASI; A03, Hardcopy
We propose that the expression of Sex Hormone- Binding Globulin (SHBG) by breast cancer cells is biologically
regulated and this SHBG functions to alter the effects of estrogens within the breast cancer cell. We have shown that plasma
protein sex hormone-binding globulin (SHBG) not only binds estrogens in plasma, but also is part of an estrogen signal
transduction system that starts with a receptor (RSHBG) for SHBG on breast cell membranes rather than the intracellular
estrogen receptor (ER). The SHBG-RSHBG complex is activated by an appropriate steroid hormone, eg. estradiol (E2),
(forming the new complex, E2-SHBG-RSHBG), to trigger a second messenger system to produce cAMP within minutes after
steroid binding. We have shown that frozen sections of normal and cancerous breast cells stain with anti-SHBG antibodies and
these same cells contain SHBG mRNA. Further, the well-known breast cancer cell line, MCF-7, contains both SHBG mRNA
and SHBG protein. The expression of SHBG by breast cancer cells raises the important question of how local regulation of
SHBG synthesis and secretion affects both sequestration of steroid hormones within the breast, and estrogen induced signal
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