Synthesis of cytokeratin 13, a component characteristic of internal stratified epithelia, is not induced in human epidermal tumors.
Human cytokeratin 13 is one of the most abundant intermediate filament (IF) proteins of many internal stratified epithelia and occurs, at least in certain cell cultures, in an O-glycosylated form binding the lectin, wheat germ agglutinin (WGA). As other groups have reported that, in the mouse, the synthesis of mRNA encoding the 47-kDa cytokeratin corresponding to human cytokeratin 13 is induced in epidermal keratinocytes during malignant transformation, we have examined the synthesis of cytokeratin 13 mRNA and protein in human epidermis and epidermal tumors, using specific cDNA probes and cytokeratin 13 antibodies. We isolated two different cDNA clones from the vulvar carcinoma cell line A-431, in which this protein is abundant: One clone seems to represent the entire mRNA, whereas the other is only a minor component and encodes a truncated cytokeratin 13 lacking most of the carboxy-terminal tail domain, probably a product of alternative, "incorrect" splicing. Comparison of the amino acid sequences with those of other cytokeratins revealed a high degree of conservation with respect to several other human type I cytokeratins, notably cytokeratin 15, and to the murine 47-kDa cytokeratin. When human epidermis and a series of benign and malignant epidermal tumors were examined with these cDNA probes and cytokeratin-13-specific antibodies we did not find an induction of expression in keratinocytes, normal or malignantly transformed, except for some scattered, sparse cytokeratin-13-positive cells and very low levels of cytokeratin 13 mRNA, detectable only with the highly sensitive polymerase chain reaction (PCR). We conclude that the gene(s) encoding cytokeratin 13 are not induced in human keratinocytes during epidermal carcinogenesis, in apparent contrast to reports of murine epidermal tumors, and we discuss possible explanations for this interspecies difference.
Kuruc
N
N
Division of Membrane Biology and Biochemistry, German Cancer Research Center, Heidelberg, Federal Republic of Germany.
Leube
R E
RE
Moll
I
I
Bader
B L
BL
Franke
W W
WW
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D004247:DNA; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D007633:Keratins; D004247:DNA