INDUCTION OF TRANSFORMING-GROWTH-FACTOR BETA-1 IN CERVICAL INTRAEPITHELIAL NEOPLASIA IN-VIVO AFTER TREATMENT WITH BETA-CAROTENE

Transforming growth factor (TGF) beta 1 is a potent growth inhibitor o f epithelial cells, Loss of responsiveness to TGF-beta 1 and/or loss o f TGF-beta 1 itself may be important in the progression of cervical in traepithelial neoplasia to invasive cervical cancer. Retinoids have an tiproliferative effects on epithelial cells and have been used as chem opreventive and chemotherapeutic agents for several human cancers. The re is evidence that retinoids exert their effects by promoting the ind uction of TGF-beta. The aim of this study was to determine whether the expression of TGF-beta 1 was altered in patients enrolled in a clinic al trial designed to test the therapeutic efficacy of beta-carotene, a carotenoid metabolized to retinol, in cervical intraepithelial neopla sia, Using an immunohistochemical technique, tissues were stained with two types of antisera that react with the intracellular and extracell ular forms of TGF-beta 1, Matched cervical biopsies taken from 10 pati ents before and after treatment with beta-carotene were immunostained simultaneously to allow direct comparison of relative staining intensi ty. A significant increase in intracellular TGF-beta 1 immunoreactivit y was noted in cervical epithelial cells in patients with cervical int raepithelial neoplasia after treatment with beta-carotene (P=0.003). T hese results demonstrate regulation of a TGF-beta isoform in vivo in h umans in response to beta-carotene administered as a chemopreventive a gent.