We have investigated the expression of the c-raf-1 proto-oncogene in neoplastic as well as hyperplastic pathologies. All small cell lung carcinomas examined express elevated levels of raf transcripts, this was particularly true of non-cultured metastases. Characterization of other surface markers revealed the presence of early monomyelocyte antigens, suggesting that these cells may have evolved from hemopoietic precursors. Activated T and B cells obtained from the peripheral blood of human autoimmune diseased individuals or from lymph nodes and spleens isolated from autoimmune mice, also expressed elevated levels of the raf proto-oncogene transcript. A human fetal liver cDNA library was screened at reduced stringency for v-raf related sequences. In addition to the expected c-raf-1 cDNA a novel sequence was isolated. Comparison of the new gene (c-pks-1) to the other raf homologs revealed nucleotide homolgies of 71%. The expression of c-pks-1 mRNA (2.8-Kb) is elevated in peripheral blood mononuclear cells isolated from patients with systemic lupus erythematosus and angioimmunoblastic lymphadenopathy with dysproteinema (AILD). In the course of localizing the c-pks-1 gene to the short arm of the X chromosome (Xpter-Xp11), another related gene (c-pks-2) was recognized and localized to chromosome 7 (7pter-7q22). The yeast homolog of raf has been cloned into Lambdagt 10 and subcloned into pBR322. Sequencing and expression studies are planned.

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Epidemiology And Genetics (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CP005426-01
Application #
4692446
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
United States
Zip Code