Retinoic acid inhibits cell growth in HPV negative cervical carcinoma cells by induction of insulin-like growth factor binding protein-5 (IGFBP-5) secretion.
Retinoids have been demonstrated to inhibit epithelial cell growth and differentiation. We examined the anti-proliferative effects of retinoic acid (RA) in an HPV positive and negative cervical carcinoma cell line. Our findings indicate that HPV-negative C33A cervical carcinoma cells are more sensitive to the growth inhibitory activity of retinoic acid (RA) than are HPV-positive CaSki cervical carcinoma cells. However, conditioned medium from RA-treated C33A cells displayed strong growth inhibitory activity in both C33A and CaSki cells. Since RA has been shown to modulate the expression of insulin-like growth factor binding proteins (IGFBPs) in many cells, we examined RA regulated expression of IGFBPs in medium isolated from RA treated C33A cells. IGFBP-5 was detectable in medium from C33A cells exposed to RA, and addition of purified exogenous IGFBP-5 resulted in growth inhibition of C33A cells. These results indicate that RA exerts it's anti-neoplastic effect in HPV negative cervical carcinoma cells via the overproduction of IGFBP-5.
Higo
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Department of Cell Biology & Anatomy, University of North Carolina, Chapel Hill 27599, USA.
Duan
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Clemmons
D R
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Herman
B
B
D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006131:Growth Inhibitors / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D027383:Papillomaviridae / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000378:metabolism / Q000473:pathology*; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014412:Tumor Virus Infections / Q000378:metabolism / Q000473:pathology*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*
D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D018975:Insulin-Like Growth Factor Binding Protein 5; D014212:Tretinoin