Localization of transforming growth factor-beta isotypes in lesions of the human breast.
Transforming growth factor-beta s (TGF-beta) comprise a highly conserved family of multifunctional cell regulatory peptides that may play a role in a variety of pathologic processes. To date, five TGF-beta isotypes have been identified, three of these in mammalian systems. A number of cultured human breast carcinoma cell lines produce biologically inactive latent TGF-beta and are growth inhibited by activated TGF-beta; TGF-beta production is estrogen-influenced in some of these cell lines. To investigate the potential role of the TGF-beta isotypes in human breast disease, we localized TGF-beta s 1, 2, and 3 immunohistochemically in normal breast, fibrocystic change, epithelial hyperplasia, sclerosing adenosis, fibroadenoma, cystosarcoma phyllodes, and several carcinoma variants. Transforming growth factor-beta s 1, 2, and 3 were identified intracellularly in most active mammary epithelia, regardless of the lesion, including carcinoma; the associated stroma contained little or no intracellular TGF-beta. An antibody that recognizes an extracellular conformation of TGF-beta stained normal intralobular stroma and, more extensively, the stroma of active fibroadenomas and low-grade phyllodes tumors and the desmoplastic stroma of carcinomas. The results indicate the potential for paracrine and autocrine regulation of the mammary gland by TGF-beta and suggest an association between TGF-beta and abnormal stromal proliferations. Altered expression of TGF-beta s 1, 2, and 3 at the protein level in mammary epithelia appears not to be a major feature of most breast lesions, raising the possibility that altered cellular response to the TGF-beta already present may play a role in the development of breast disease.
McCune
B K
BK
Laboratory of Chemoprevention, National Cancer Institute, Bethesda, MD.
Mullin
B R
BR
Flanders
K C
KC
Jaffurs
W J
WJ
Mullen
L T
LT
Sporn
M B
MB
D001940:Breast / Q000737:chemistry*; D001941:Breast Diseases / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000737:chemistry / Q000473:pathology; D005260:Female; D006801:Humans; D007106:Immune Sera; D007124:Immunoenzyme Techniques; D016212:Transforming Growth Factor beta / Q000032:analysis* / Q000276:immunology
D007106:Immune Sera; D016212:Transforming Growth Factor beta