K-FGF mediated transformation and induction of metastatic potential involves altered ornithine decarboxylase and S-adenosylmethionine decarboxylase expression--role in cellular invasion.
Omithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) expression was investigated in NIH-3T3 fibroblasts that secrete K-FGF. Correlations between altered ODC and SAMDC expression and malignant potential were determined. Increased ODC and SAMDC expression was associated with increased expression of both ODC and SAMDC mRNA and enzyme activity levels. Transcriptional and post-transcriptional regulatory mechanisms were found to account for the increased expression of both ODC and SAMDC. Amplification of the ODC gene also played a role. Correlations between the expression of ODC and the invasion ability of the K-FGF overexpressing cells were also found. Additionally, putrescine, which is a cellular polyamine, was found to play a role in determining the nature of the invasive capacity of the K-FGF overexpressing cells. The results of this study which established correlations between alterations in the expression of ODC and SAMDC, the key rate limiting and regulatory activities in the synthesis of cellular polyamines, and malignant potential as a consequence of K-FGF overexpression supports a model which suggests that growth factor modulation of ODC and SAMDC expression is part of the altered growth regulatory program associated with cellular transformation and malignant progression.
Hardin
Marcus S
MS
Department of Laboratory Medicine and Pathobiology, St. Michael's Hospital, University of Toronto, ON, Canada.
Mader
Rene
R
Hurta
Robert A R
RA
D016475:3T3 Cells / Q000187:drug effects / Q000201:enzymology; D012437:Adenosylmethionine Decarboxylase / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D051379:Mice; D009955:Ornithine Decarboxylase / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011700:Putrescine / Q000494:pharmacology; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection; D014170:Transformation, Genetic; D015854:Up-Regulation
C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D005346:Fibroblast Growth Factors; D003094:Collagen; D009955:Ornithine Decarboxylase; D012437:Adenosylmethionine Decarboxylase; D011700:Putrescine