Human squamous-cell-carcinoma cell line (DJM-1) cells synthesize P-cadherin molecules via an elevation of extracellular calcium: calcium regulates P-cadherin-gene expression at the translational level via protein tyrosine phosphorylation.
Spatially-regulated P-cadherin expression is crucial for maintaining the normal epidermal architecture. P-cadherin expression in cutaneous squamous-cell carcinomas (SCC) is altered, and may participate in tumor progression. We therefore investigated how P-cadherin expression was regulated in a cultured cutaneous SCC cell line (DJM-1). At low calcium concentration (0.05 mM), DJM-1 cells expressed P-cadherin weakly in the cytoplasm. At a higher calcium concentration, P-cadherin was promptly translocated to the cell surface within 30 min, gradually increased on the cell surface for up to 48 hr, and was continuously expressed for at least 7 days. During this time course, the total amount of P-cadherin protein had increased, whereas the steady-state mRNA levels for P-cadherin had not changed. The inhibition of protein synthesis by cycloheximide, but not the inhibition of gene transcription by actinomycin-D, completely suppressed the expression of P-cadherin. The effect of calcium was inhibited by tyrphostins but not by H-7, cholera toxin, or dibutylic cyclic AMP. Increments in the extracellular calcium concentration did not mobilize the intracellular calcium pool, and were accompanied by the tyrosine phosphorylation of a 62-kDa protein. In addition, DJM-1 cells expressed mRNA for a calcium-sensing receptor originally demonstrated in the parathyroid gland. The results suggest an unique mechanism for regulating P-cadherin gene expression in DJM-1 cells by extracellular calcium, which stimulates the de novo synthesis of P-cadherin at the translational level through protein tyrosine phosphorylation.
Wakita
H
H
Department of Dermatology, Hamamatsu University School of Medicine, Japan. wakita@hama-med.ac.jp
Furukawa
F
F
Baba
S
S
Takigawa
M
M
D001483:Base Sequence; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D002118:Calcium / Q000008:administration & dosage*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D015820:Cadherins; D002135:Calcium-Binding Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D019000:Phosphotyrosine; D002118:Calcium