Transforming growth factors-beta are not good biomarkers of chemopreventive efficacy in a preclinical breast cancer model system.
Using a carcinogen-initiated rat model of mammary tumorigenesis, we tested the hypothesis that transforming growth factor (TGF)-betas are useful biomarkers of chemopreventive efficacy in the breast. The chemopreventive agents tested were tamoxifen and the retinoids 9-cis-retinoic acid (9cRA) and N-(4-hydroxyphenyl)retinamide (4-HPR), because both antiestrogens and retinoids have previously been shown to upregulate TGF-betas in vitro. Despite demonstrable chemopreventive efficacy in this model, none of these agents, alone or in combination, had any significant impact on the expression of TGF-betas in the mammary ductal epithelium or periductal stroma as determined by immunohistochemistry. These data suggest that TGF-betas are not likely to be useful biomarkers of chemopreventive efficacy in a clinical setting.
Zujewski
J
J
Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Vaughn-Cooke
A
A
Flanders
K C
KC
Eckhaus
M A
MA
Lubet
R A
RA
Wakefield
L M
LM
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018890:Chemoprevention; D005260:Female; D005819:Genetic Markers / Q000502:physiology; D007124:Immunoenzyme Techniques; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced* / Q000517:prevention & control* / Q000628:therapy; D008958:Models, Molecular; D011372:Progestins / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012176:Retinoids / Q000627:therapeutic use; D013629:Tamoxifen / Q000627:therapeutic use; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D000970:Antineoplastic Agents; D005819:Genetic Markers; D011372:Progestins; D012176:Retinoids; D016212:Transforming Growth Factor beta; D013629:Tamoxifen