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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
Author(s) -
Wakita Hisashi,
Furukawa Fukumi,
Baba Satoshi,
Takigawa Masahiro
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19971104)73:3<432::aid-ijc19>3.0.co;2-e
Subject(s) - tyrosine phosphorylation , extracellular , calcium , cadherin , phosphorylation , calcium in biology , biology , microbiology and biotechnology , cell culture , gene expression , cell , endocrinology , intracellular , medicine , biochemistry , gene , genetics
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. Int. J. Cancer 73:432–439, 1997. © 1997 Wiley‐Liss, Inc.