Induction of transforming growth factor beta 1 in human breast cancer in vivo following tamoxifen treatment.
We have investigated the ability of tamoxifen to regulate members of the transforming growth factor beta (TGF-beta) family in human breast cancers in vivo. Using immunohistochemical techniques, we find that 3 months of tamoxifen treatment causes a consistent induction of extracellular TGF-beta 1 in breast cancer biopsies, compared with matched pretreatment samples from the same patient. The induced TGF-beta is localized between and around stromal fibroblasts and appears to be derived from these cells. Lower levels of TGF-beta 1,-beta 2, and -beta 3 seen in epithelial cells were not altered by tamoxifen treatment. The increased stromal staining of TGF-beta 1 occurred in estrogen receptor-negative as well as estrogen receptor-positive tumors. These results provide in vivo evidence for a novel, estrogen receptor-independent mechanism of action for tamoxifen, involving the stromal induction of a potent growth inhibitor for epithelial cells.
Butta
A
A
Hartwell Laboratory Royal Marsden Hospital, London, United Kingdom.
MacLennan
K
K
Flanders
K C
KC
Sacks
N P
NP
Smith
I
I
McKinna
A
A
Dowsett
M
M
Wakefield
L M
LM
Sporn
M B
MB
Baum
M
M
D014408:Biomarkers, Tumor / Q000032:analysis; D001706:Biopsy; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D011960:Receptors, Estrogen / Q000032:analysis; D013629:Tamoxifen / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D016212:Transforming Growth Factor beta; D013629:Tamoxifen