Induction of 18A2/mts1 gene expression and its effects on metastasis and cell cycle control.
The metastasis associated 18A2/mtsI gene was inserted into the mammalian expression vector pMAMneo placing it under the control of the dexamethasone-inducible MMTV promoter. The construct was transfected into dexamethasone receptor negative F1 and receptor positive F10 cells of the B16 murine melanoma. The transferred gene was switched on in two transfectant clones of F10, by exposure to 10(-6) M dexamethasone, but not in clones of the receptor negative F1 line. One of the F10 transfectant clones (F10-192/10) was characterized further. A 13.5-fold increase in 18A2/mts1 transcripts was found in this clone upon exposure to dexamethasone. There was also a seven-fold increase in lung colonization in an experimental metastasis assay, together with increased expression of depolymerized tubulin and enhanced detection of p53 protein. The number of cells in the S phase increased by 2.5-fold following dexamethasone treatment of the clone. These data suggest a direct involvement of the 18A2/mts1 gene in lung colonization by the tumor cells. The 18A2/mts1 protein promotes tubulin depolymerization, sequesters the p53 phosphoprotein, and induces the cells to enter the S phase, but the relevance of these in the metastatic process remains to be elucidated.
Parker
C
C
Cancer Research Unit, University of Newcastle upon Tyne, Medical School, UK.
Whittaker
P A
PA
Usmani
B A
BA
Lakshmi
M S
MS
Sherbet
G V
GV
D000818:Animals; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics*; D002460:Cell Line; D017931:DNA Primers; D003907:Dexamethasone / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis / Q000235:genetics*; D009418:S100 Proteins; D014162:Transfection; D014404:Tubulin / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D002135:Calcium-Binding Proteins; D017931:DNA Primers; D009418:S100 Proteins; D014404:Tubulin; D016159:Tumor Suppressor Protein p53; D003907:Dexamethasone