Induction of transforming growth factor β-1 in cervical intraepithelial neoplasia in vivo after treatment with β-carotene

Transforming growth factor (TGF) β1 is a potent growth inhibitor of epithelial cells. Loss of responsiveness to TGF-β1 and/or loss of TGF-β1 itself may be important in the progression of cervical intraepithelial neoplasia to invasive cervical cancer. Retinoids have antiproliferative effects on epithelial cells and have been used as chemopreventive and chemotherapeutic agents for several human cancers. There is evidence that retinoids exert their effects by promoting the induction of TGF-β. The aim of this study was to determine whether the expression of TGF-β1 was altered in patients enrolled in a clinical trial designed to test the therapeutic efficacy of β-carotene, a carotenoid metabolized to retinol, in cervical intraepithelial neoplasia. Using an immunohistochemical technique, tissues were stained with two types of antisera that react with the intracellular and extracellular forms of TGF-β1. Matched cervical biopsies taken from 10 patients before and after treatment with β-carotene were immunostained simultaneously to allow direct comparison of relative staining intensity. A significant increase in intracellular TGF-β1 immunoreactivity was noted in cervical epithelial cells in patients with cervical intraepithelial neoplasia after treatment with β-carotene (P = 0.003). These results demonstrate regulation of a TGF-β isoform in vivo in humans in response to β-carotene administered as a chemopreventive agent.