Cell Growth & Differentiation, Vol 4, Issue 9 723-729, Copyright © 1993 by American Association of Cancer Research

ARTICLES

Phorbol esters regulate preprogastrin-releasing peptide messenger RNA in small cell lung cancer cells

M Draoui, TW Moody, Z Fathi and J Battey
Department of Biochemistry and Molecular Biology, George Washington University Medical Center, Washington, D.C. 20037.

The expression of preprogastrin-releasing peptide (GRP) mRNA was studied using human small cell lung cancer (SCLC) cells. By Northern analysis, preproGRP mRNA was stimulated by 4 beta-phorbol 12-myristate 13 alpha-acetate (PMA) in a concentration- and time-dependent manner in these cells. In cell line NCI-H209, the addition of 10(-6) M PMA increased a 0.9-kb mRNA after 8 h. An inactive phorbol ester, 4 alpha-PMA, had little effect on preproGRP mRNA. A nuclear run-on assay indicated that 10(-6) M PMA increased preproGRP transcription 3-fold, whereas beta-actin and glyceraldehyde 3-phosphate dehydrogenase transcription was unaltered. In contrast, PMA had little effect on beta-actin mRNA expression. PMA (1 microM) in the presence of 100 microM 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7), a protein kinase C inhibitor, had little effect on preproGRP mRNA. Addition of PMA after protein kinase C down-regulation did not alter preproGRP mRNA. PMA (1 microM) caused translocation of protein kinase C from the cytosol to the membrane of SCLC cells. Also, PMA (10(-6) M) stimulated and H7 (10(-4) M) reduced SCLC growth in vitro. When new synthesis of preproGRP mRNA was blocked by the addition of actinomycin D, preproGRP mRNA remained stable for 15 h. These data suggest that PMA induces transcription of GRP mRNA in SCLC cells.

This article has been cited by other articles:

				A. M. Bajo, A. V. Schally, M. Krupa, F. Hebert, K. Groot, and K. Szepeshazi Bombesin antagonists inhibit growth of MDA-MB-435 estrogen-independent breast cancers and decrease the expression of the ErbB-2/HER-2 oncoprotein and c-jun and c-fos oncogenes PNAS, March 19, 2002; 99(6): 3836 - 3841. [Abstract] [Full Text] [PDF]

				L. Paolucci and E. Rozengurt Protein Kinase D in Small Cell Lung Cancer Cells: Rapid Activation through Protein Kinase C Cancer Res., February 1, 1999; 59(3): 572 - 577. [Abstract] [Full Text] [PDF]

				K. J. Haley, K. Patidar, F. Zhang, R. L. Emanuel, and M. E. Sunday Tumor necrosis factor induces neuroendocrine differentiation in small cell lung cancer cell lines Am J Physiol Lung Cell Mol Physiol, August 1, 1998; 275(2): L311 - L321. [Abstract] [Full Text] [PDF]