Extinction of liver/bone/kidney alkaline phosphatase in osteosarcoma hybrid cells.
We have constructed a series of interspecific somatic cell hybrids between the human osteoblast-like osteosarcoma, TE85, and a mouse fibrosarcoma, La-t-. In these whole-cell hybrids, we observed a 10-fold reduction of human liver/bone/kidney (L/B/K) alkaline phosphatase steady-state mRNA and alkaline phosphatase protein activity. The phenomenon of loss of tissue-specific gene expression has been termed extinction. Subclones of these hybrids were isolated, which reexpressed the alkaline phosphatase gene product. These late-passage hybrids had a reduced number of mouse fibroblast chromosomes when compared to earlier passages. This suggests that a trans-acting negative regulatory element, encoded in the fibroblast genome, regulates expression of L/B/K alkaline phosphatase. This is the first evidence that extinction plays a role in the regulation of osteoblast gene expression.
Johnson-Pais
T L
TL
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284.
Leach
R J
RJ
D000469:Alkaline Phosphatase / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic; D005796:Genes; D006801:Humans; D006822:Hybrid Cells; D017404:In Situ Hybridization, Fluorescence; D066298:In Vitro Techniques; D007621:Karyotyping; D051379:Mice; D010006:Osteoblasts / Q000201:enzymology*; D012516:Osteosarcoma / Q000201:enzymology*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000469:Alkaline Phosphatase