Transformation of revertant murine cells by 5-azacytidine results in rapid inhibition of lysyl oxidase expression.
Lysyl oxidase (LO) is synthesized intracellularly as a proenzyme that is secreted and then processed extracellularly to a mature form. LO is expressed in NIH3T3 cells, but only very low levels are observed after NIH 3T3 is transformed by c-H-ras or one of several other oncogenes. LO functions as a tumor suppressor. Treatment of ras-transformed cells with interferon-alpha with or without retinoic acid results in their persistent reversion to a non-transformed state that is dependent on the restoration of LO expression. When such revertant cells are treated with 5-azacytidine (5-azaC), they undergo rapid morphological retransformation. Within one passage after addition of 5-azaC, there was a down regulation of LO mRNA and proenzyme protein. These data suggest a direct relationship between the transformed state and LO expression.
Yeh
Tze-Jou Annie
TJ
Department of Pathology and the United States Military Cancer Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Contente
Sara
S
Friedman
R M
RM
D000818:Animals; D001374:Azacitidine / Q000494:pharmacology*; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras / Q000235:genetics / Q000502:physiology; D051379:Mice; D041681:NIH 3T3 Cells; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics* / Q000378:metabolism*; D013997:Time Factors
D008249:Protein-Lysine 6-Oxidase; D001374:Azacitidine