[Establishment and characterization of a renal carcinoma cell line producing erythropoietin (effects of cyclic AMP on erythropoietin production in vitro)].
METHODS
A cell line obtained from a primary lesion of renal cell carcinoma was newly established and observed to produce erythropoietin (Ep) continuously in vivo as well as in vitro. The histopathological and biological characteristics of this cell line were then analyzed in parallel with a study initiated on the role of cAMP on Ep production.


RESULTS
The cells were subsequently serially transplanted into nude mice. The levels of Ep and hematocrit in the mice were found to correlate very closely with the tumor size. The histology of the xenograft was similar to the original tumor cells which constituted a nearly clear cell type and was immunostained positively for Ep. Ultrastructurally, Ep was localized in the perinuclear space, with part of the rough surface of the endoplasmic reticulum. In vitro, the cells grew exponentially with an approximate population doubling time of 2 days. The mRNA of Ep was detected using the RT-PCR method. The number of chromosomes in the cells ranged from 117 to 147 and featured complicated rearrangements and marker chromosomes. Forskolin, a well-known activator of adenylate cyclase which in turn generated the accumulation of cyclic AMP, produced a significant dose-related enhancement of Ep biosynthesis both in the cells and in the spent culture medium.


CONCLUSIONS
Based on the results derived from the foregoing analysis of this new cell line, cAMP was found to play a salient role both in Ep biosynthesis as well as in Ep release.
Tanomogi
H
H
Department of Urology, School of Medicine, Keio University.
D000368:Aged; D000818:Animals; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D000242:Cyclic AMP / Q000494:pharmacology* / Q000502:physiology; D004921:Erythropoietin / Q000096:biosynthesis*; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004921:Erythropoietin; D000242:Cyclic AMP