Regulation of Osteoblast Gene Expression in Intratypic Osteosarcoma Hybrid Cells

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Intratypic osteosarcoma hybrids were constructed by fusing the human osteoblast-like osteosarcoma SaOS-2 with the rat osteoblast-like osteosarcoma UMR-106. Both of these osteosarcomas express liver/bone/kidney alkaline phosphatase (ALPL), but only the UMR-106 cell line expresses osteopontin (OPN), a gene expressed during later stages of osteoblast differentiation. Analysis of osteoblast gene expression in these hybrids demonstrated that ALPL continued to be expressed; however, OPN steady-state mRNA levels were dramatically reduced in four hybrids. Quantitative measurements indicated theft OPN steady-state mRNA levels were extinguished by a factor of 20- to 1000-fold. Since SaOS-2 chromosomes are preferentially lost from these hybrids, subclones of extinguished hybrids were isolated that reexpressed OPN mRNA at levels similar to the UMR-106 parental line. These data indicate that trans-acting negative regulatory factors, expressed from the SaOS-2 genome, are responsible for OPN extinction. This report provides the first demonstration of the negative regulation of OPN gene expression and also provides additional evidence that extinction plays a role in the regulation of osteoblast gene expression.

Original languageEnglish (US)
Pages (from-to)370-376
Number of pages7
JournalExperimental Cell Research
Issue number2
StatePublished - Dec 1995

ASJC Scopus subject areas

  • Cell Biology

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