REGULATION OF GENE-TRANSCRIPTION AND PROLIFERATION BY PARATHYROID-HORMONE IS BLOCKED IN MUTANT OSTEOBLASTIC CELLS RESISTANT TO CYCLIC-AMP

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:87

Article

ZAJAC, JD ; KEARNS, AK ; SKURAT, RM ; KRONENBERG, HM ; BRINGHURST, FR

关键词: PARATHYROID HORMONE;    CYCLIC AMP;    OSTEOSARCOMA CELLS (RAT);    SIGNAL TRANSDUCTION;    PROLIFERATION;    PROTEIN KINASE-A;   

DOI  :  10.1016/0303-7207(92)90234-W

来源: Elsevier

【 摘 要 】

We employed a cyclic AMP-resistant subclone of UMR 106-01 osteoblastic osteosarcoma cells (UMR 4-7) with a regulated, dominant-negative mutation of cyclic AMP-dependent protein kinase (PK-A), to examine the mechanism(s) whereby parathyroid hormone (PTH) regulates growth of these cells. Expression of a transiently transfected CAT reporter gene controlled by the cAMP response element of the rat somatostatin gene ('SST-CAT') was used to monitor PK-A activation in intact cells. Agonist-stimulated SST-CAT expression was specific for agents known to activate adenylate cyclase, required an intact cAMP response element and was specifically blocked following induction of the mutant cAMP-resistant phenotype in UMR 4-7 cells. Inhibition of the proliferation of UMR 106-01 cells by PTH, which is mimicked by forskolin and 8-bromo-cAMP, was blocked completely in mutant cyclic AMP-resistant UMR 4-7 cells. We conclude that control of proliferation in UMR 106-01 cells by PTH involves the cAMP messenger system and requires activation of PK-A.

【 授权许可】

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