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Department of Chemical Pathology [N. H. H., V. P. M., D. A., T. J. M.] and Pathology [J. R. S.], University of Sheffield Medical School, Beech Hill Road, Sheffield, S10 2RX, and Department of Urology, Royal Hospital, West Street, Sheffield, 1, England[J. C. H.]
Tissue morphology and adenylate cyclase activity have been studied in 23 consecutive patients with renal cortical carcinoma. Electron microscopy and examination of glycogen distribution demonstrated that tumors were composed either of cells with predominantly proximal tubular cell characteristics or of cells with distal tubular cell characteristics. Light microscopy was not sultable for this classification.
Basal (unstimulated) adenylate cyclase activity in membranes prepared from control uninvolved renal cortex was 155 ± 25 (mean ± S.E.; n, 19) pmoles cyclic adenosine 3':5'-monophosphate (cyclic AMP) per mg protein per 15 min. In tumors with proximal characteristics, the basal adenylate cyclase activity was 754 ± 120 (n, 14) and, in those with distal characteristics, 247 ± 32 (n, 4) pmoles cyclic AMP per mg protein per 15 min. Adenylate cyclase activity in control tissue was stimulated by parathyroid hormone, prostaglandins E1 and E2, glucagon, and sodium fluoride. Tumor adenylate cyclase responded poorly and infrequently to parathyroid hormone, responded subnormally to prostaglandins E1 and E2 and sodium fluoride, and did not respond to glucagon. Thus, both basal adenylate cyclase activity and the hormone responsiveness of the enzyme had been modified in the established tumor.
The data indicate that high rates of cyclic AMP production may occur in malignant cells, an observation that has been made, to the present time, with several in vivo tumors. This differs from much, published in vitro evidence that associates malignant transformation with low adenylate cyclase activity and cellular cyclic AMP levels.
1 This work was supported by grants from the Medical Research Council and the Yorkshire Council of the Cancer Research Campaign.
2 To whom requests for reprints should be addressed, at Department of Medicine, University of Melbourne, Repatriation General Hospital, Heidelberg, 3084, Victoria, Australia.
Received 7/ 5/77. Accepted 10/ 5/77.
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