Role of transforming growth factor beta in breast carcinogenesis.

Transforming growth factor (TGF) beta is a pre-eminent negative growth regulator that has antiproliferative effects on a range of epithelial cells. This ability has evoked interest in this growth factor as a tumour suppressor with potential clinical significance. In the early stages of breast carcinogenesis, a growth-inhibitory response to TGFbeta is maintained, which depends on an intact TGFbeta signalling pathway. Tumour development and progression of cells along a neoplastic continuum is accompanied by loss of this growth-inhibitory response to TGFbeta, which might instead promote tumour growth indirectly through a combination of permissive effects on stromal tissue, angiogenesis, and the immune system. This review discusses the complexity of functional pleiotropy and the continually changing roles of TGFbeta as a tumour evolves, along with competing therapeutic strategies. The boosting of local endogenous amounts of TGFbeta in conjunction with enhancement of cellular responsiveness might be appropriate in early malignant disease, and anti-TGFbeta approaches could yield a therapeutic gain in metastatic states.