Restoration of differentiation and suppression of tumorigenicity in somatic cell hybrids of human squamous carcinoma cells and keratinocytes.
Somatic cell hybrid cell lines derived from the fusion of human squamous carcinoma cells (FaDu-Hyg) with human keratinocytes were used to examine the relationships between cell differentiation and tumorigenicity. Treatment of the parental keratinocytes or the two hybrid cell lines with the combination of calcium and fetal bovine serum increased the expression of the envelope precursor, involucrin, 4- to 8-fold, whereas it remained unchanged in FaDu-Hyg cells. Similarly, calcium- and serum-treated keratinocytes and the two hybrid cell lines displayed a 7- to 13-fold increase of the activity of membrane-associated type I transglutaminase, whereas transglutaminase activity in FaDu-Hyg cells did not change appreciably. FaDu-Hyg cells were tumorigenic in vivo, but tumorigenicity was suppressed in both hybrid cell lines. Analysis of additional tumor cell lines indicated that the expression of transglutaminase I and involucrin are under separate genetic control and that loss of transglutaminase activity can result either from a lack of protein or from a defect in the activation step. Thus, keratinization of squamous epithelial cells appears to be controlled by several different recessive genes, which cosegregate with but are probably only partly identical with the genes that suppress tumor formation in vivo.
Fynan
T M
TM
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520.
Morgan
D
D
Yuspa
S H
SH
Longley
B J
BJ
Zhou
Z L
ZL
Reiss
M
M
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002417:Cattle; D002454:Cell Differentiation; D002459:Cell Fusion; D002460:Cell Line; D003470:Culture Media; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006822:Hybrid Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015603:Keratinocytes; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011498:Protein Precursors / Q000096:biosynthesis*; D011503:Transglutaminases / Q000032:analysis / Q000096:biosynthesis; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D003470:Culture Media; D011498:Protein Precursors; C032253:involucrin; D011503:Transglutaminases; D002118:Calcium