DOWN-REGULATION OF SPARC OSTEONECTIN BM-40 EXPRESSION IN METHYLCHOLANTHRENE-INDUCED FIBROSARCOMAS AND IN KIRSTEN-MSV TRANSFORMED FIBROBLASTS

SPARC (secreted protein acid and rich in cysteine), also known as osteonectin or BM-40, is a glycoprotein associated with the extracellular matrix of bone as well as with many soft tissues that produce extracellular matrix, including matrix-producing tumours. Northern and slot-blot analyses were used to study SPARC expression in tumours induced in vivo by methylcholanthrene (MCA) and in transformed cells induced in vitro by Kirsten-MSV and SV-40 infection. MCA-induced tumours expressed SPARCmRNA at quantitatively different levels. Fibroblasts transformed in vitro by Kirsten-MSV, and, to a lesser extent, by SV-40, showed reduced levels of SPARCmRNA expression compared with normal fibroblasts. Run-on assay indicated that transcription of SPARC was lower in the Kirsten-MSV transformed cells than in the normal parental fibroblast culture. However, SPARCmRNA in the transformed culture was as stable as that in normal culture. The difference, therefore, between levels of SPARCmRNA in transformed and normal culture was mainly due to different rates of transcription. Cloned cell lines derived from the Kirsten-MSV transformed culture also showed heterogeneous expression of SPARC: two lines had high and two had low expression of the gene. The level of mRNA correlated with that of the protein secreted. The SPARC expression might contribute to the malignant phenotype.