HEMATOLOGICAL ONCOLOGY, VOL. I, 61-75 (1983) CHARACTERIZATION OF THE EXPRESSION OF CELLULAR RETROVIRUS GENES AND ONCOGENES IN FELINE CELLS MICHAEL P. BUSCH*, B. GAYATHRI DEVI*, LISA HOKAMA zyxwvu SOE*, BERNARD PERBAL~, MARCEL A, BALUDA~ AND PRADIP ROY-BURMAN*$$ zyxwv Department ofPatholog.v* and Biochemistr.y$. University ofSouthern California School ofMedicine, Los .hgeles, California 90033, and University ofCalifornia at Los Angeles School ofMedicine and Jonsson Comprehensive Cancer Centerf. Los Angeles. Califarnia 90024. U.S.A. SUMMARY Expression of endogenous retrovirus genes and two different cellular oncogenes (c-onc genes) was examined at the transcriptional level in a variety of normal and lymphoma/leukemia tissues of the domestic cat. The two oncogenes, c-myb(re1ated to avian myeloblastosis virus) and c-myc(re1ated to avian myelocytomatosis virus) were selected for their association with the induction of hematopoietic malignancies, when present in the transforming retroviruses. Tissue-specific expression of endogenous feline leukemia virus (FeLV)-related genes was detected in cellular subpopulations of the cat placenta by zyxwvutsr in situ method of hybridization. Gel blotting analysis of placental poly(A)-selected RNA revealed that the FeLV-related RNA species were primarily subgenomic, representing the env gene region of the endogenous provirus elements. Like the endogenous retrovirus genes, c-myb and c-myc loci ofthe cat genomic DNA were also transcribed at differential levels in normal tissues of the cat. Dot-blot hybridization analysis showed that the expression of these two oncogenes was linked to growth and development as it varied with the gestational age of the fetus and from fetal to adult tissues. Among the major hematopoietic organs, spleen and bone marrow contained both c-myb and c- myc transcripts, while thymus preferentially expressed the c-mvb gene. In contrast to the low level of c-myc expression in fetal thymus tissues, enhanced c-myc expression was detected in all five thymomas tested and also in several other neoplasms including two granulocytic leukemias. The feline c-mvb gene was not very active in granulocytic leukemias or in three of the five thymomas. RNA gel blotting analysis of poly(A)-selected RNA of a thymoma and its lymph node metastasis showed identical pattern of c-myc transcripts. KEY WORDS Endogenous feline leukemia virus genes Feline c-myb oncogene Feline c-m.vc oncogene Feline lymphoma/leukemias Oncogenes and embryonic tissues INTRODUCTION In the outbred domestic cat there is a high incidence of leukemia* naturally associated with the horizontal infection of a replication-competent ecotropic retrovirus, feline leukemia virus (FeLV), which apparently does not encode a transforming gene. Cats free of infectious FeLV also develop leukemias whose incidence represents about one-third of the naturally §Addressee for correspondence. *The term ‘leukemia’ is used here in the broad, rather than the narrow sense to describe leukemia-lymphoma complex in general. zyxwvutsrq 0278-0232/83/010061-15$01.50 zyxwvu 0 1983 by John Wiley & Sons, Ltd. Received I I August I982 Accepted 20 August I982