Differences in keratin synthesis between normal epithelial cells and squamous cell carcinomas are mediated by vitamin A.
A number of recent studies have indicated that the expression of keratins is altered upon malignant transformation of human epithelial cells. We have shown that the altered expression of 67-kDa and 40-kDa keratins in established squamous cell carcinoma lines from tongue and epidermis stems largely from a difference in their sensitivity to vitamin A apparently acquired during tumorigenesis. When the vitamin A concentration in the medium is raised, the 40-kDa keratin is produced at increased levels. Conversely, when the amount of vitamin is reduced, the 67-kDa keratin is synthesized and the cells undergo stratification and terminal differentiation. However, even when vitamin A is quantitatively removed from the medium, the maximal degree of differentiation attained by each squamous cell carcinoma cell as judged by the synthesis of 67-kDa keratin was still less than that of the normal keratinocytes. These findings suggest that the altered patterns of keratins observed for some tissues upon malignant transformation arise from a complex mixture of intracellular changes in the differentiative pathway in addition to changes in the responsiveness of cells to extracellular regulators of keratin gene expression.
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007231:Infant, Newborn; D007633:Keratins / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D018168:Receptors, Retinoic Acid; D000084562:Retinyl Esters; D014801:Vitamin A / Q000031:analogs & derivatives / Q000494:pharmacology; D014802:Vitamin A Deficiency / Q000378:metabolism*
D002352:Carrier Proteins; D004224:Diterpenes; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D000084562:Retinyl Esters; D014801:Vitamin A; C009166:retinol acetate; D007633:Keratins