Constitutive and Cell Cycle Regulated Expression of c-myc mRNA is Related to the State of Differentiation in Murine B-Lymphoid Tumors

Abstract

The c-myb proto-oncogene encodes a nuclear, DNA binding protein (Klempnauer 1984; Luscher 1990) which has recently been shown to have the ability to act as a transcriptional transactivator (Westin 1989). The expression of c-myb mRNA has been predominantly associated with normal tissue and tumor cell lines of immature hematopoietic origin (Westin 1982; Gonda 1982) and the chemically induced differentiation of several hematopoietic tumor cell lines in vitro results in the down-regulation of c-myb mRNA levels (Gonda 1984; Kirsch 1986). In addition, c-myb expression has recently been reported to be down-regulated in neuroblastomas which were induced to differentiate with retinoic acid (Thiele 1988). We have previously shown in murine B-lymphoid tumors that pre-B cell lymphomas contain 10 to greater than 100 fold more c-myb mRNA than B cell lymphomas and plasmacytomas (Bender 1987a) and that this difference is maintained primarily by a premature block to transcription elongation (attenuation) which occurs in the first intron of the c-myb gene (Bender 1987b). Attenuation has also been shown to be involved in the regulation of c-myb mRNA levels during the chemically induced differentiation of a murine erythroleukemia cell line (Watson 1988). We have recently examined the basis for high versus low level expression of c-myb mRNA in murine B-lymphoid tumors and report that pre-B cell lymphomas constitutively express c-myb mRNA while B cell lymphomas regulate c-myb mRNA levels during the cell cycle. In addition, we describe a protein/DNA interaction, detected near the putative site of attenuation, that correlates with active attenuation in these tumor cell lines.