Cell Growth & Differentiation, Vol 6, Issue 9 1111-1118, Copyright © 1995 by American Association of Cancer Research

ARTICLES

Interleukin 4 down-regulates expression of c-kit and autocrine stem cell factor in human colorectal carcinoma cells

H Lahm, P Amstad, A Yilmaz, Z Borbenyi, J Wyniger, JR Fischer, L Suardet, JC Givel and N Odartchenko
Swiss Institute for Experimental Cancer Research, Department of Cellular Biology, Epalinges, Switzerland.

Stem cell factor (SCF) is a cytokine which plays an important role in the development of precursor cells. We have investigated the expression of SCF and its receptor, the c-kit proto-oncogene, in human colorectal carcinoma cell lines. Using reverse transcription-PCR, we confirmed the expression of c-kit in two lines (LS174T and LS1034) and of SCF in 9 of 11 cell lines tested. In a Northern blot, a single transcript of 6.6 kb was detected for SCF mRNA. In addition, two lines (LS174T and HT29) synthesized SCF protein, as detected by Western blot analysis. SCF stimulated proliferation and colony formation of LS174T in a dose-dependent manner up to 160%. A half-maximal effect was obtained with about 5.5 ng/ml of SCF under both growth conditions. LS174T cells expressed the M(r) 145,000 c-kit protein on the cell surface and a neutralizing anti-c-kit mAb inhibited colony formation of LS174T by 40%. Interleukin 4 (IL-4) completely inhibited SCF-induced proliferation of LS174T cells. Interestingly, IL-4 induced an almost complete down-regulation of both c-kit and SCF expression in LS174T. Our findings suggest that in LS174T cells, an SCF-mediated autocrine loop is functional and that IL-4 down-regulates the expression of both the receptor and the ligand of this circuit.

This article has been cited by other articles:

				R. Yorke, M. Chirala, and M. Younes c-Kit Proto-Oncogene Product Is Rarely Detected in Colorectal Adenocarcinoma J. Clin. Oncol., October 15, 2003; 21(20): 3885 - 3886. [Full Text] [PDF]

				R. D. Blumenthal, A. Reising, E. Leon, and D. M. Goldenberg Modulation of Marrow Proliferation and Chemosensitivity by Tumor-produced Cytokines from Syngeneic Pancreatic Tumor Lines Clin. Cancer Res., May 1, 2002; 8(5): 1301 - 1309. [Abstract] [Full Text] [PDF]

				N Nagy, Y Bronckart, I Camby, H Legendre, H Lahm, H Kaltner, Y Hadari, P Van Ham, P Yeaton, J-C Pector, et al. Galectin-8 expression decreases in cancer compared with normal and dysplastic human colon tissue and acts significantly on human colon cancer cell migration as a suppressor Gut, March 1, 2002; 50(3): 392 - 401. [Abstract] [Full Text] [PDF]

				G. Bellone, A. Carbone, N. Sibona, O. Bosco, D. Tibaudi, C. Smirne, T. Martone, C. Gramigni, M. Camandona, G. Emanuelli, et al. Aberrant Activation of c-kit Protects Colon Carcinoma Cells against Apoptosis and Enhances Their Invasive Potential Cancer Res., March 1, 2001; 61(5): 2200 - 2206. [Abstract] [Full Text]

				L. Landuzzi, C. De Giovanni, G. Nicoletti, I. Rossi, C. Ricci, A. Astolfi, L. Scopece, K. Scotlandi, M. Serra, G. P. Bagnara, et al. The Metastatic Ability of Ewing's Sarcoma Cells Is Modulated by Stem Cell Factor and by Its Receptor c-kit Am. J. Pathol., December 1, 2000; 157(6): 2123 - 2131. [Abstract] [Full Text] [PDF]

				P. Mirmonsef, C. P. Shelburne, C. Fitzhugh Yeatman II, H. J. Chong, and J. J. Ryan Inhibition of Kit Expression by IL-4 and IL-10 in Murine Mast Cells: Role of STAT6 and Phosphatidylinositol 3'-Kinase J. Immunol., September 1, 1999; 163(5): 2530 - 2539. [Abstract] [Full Text] [PDF]

				S. C. Bischoff, G. Sellge, A. Lorentz, W. Sebald, R. Raab, and M. P. Manns IL-4 enhances proliferation and mediator release in mature human mast cells PNAS, July 6, 1999; 96(14): 8080 - 8085. [Abstract] [Full Text] [PDF]

				M. M. Weber, C. Fottner, P. Schmidt, K. M. H. Brodowski, K. Gittner, H. Lahm, D. Engelhardt, and E. Wolf Postnatal Overexpression of Insulin-Like Growth Factor II in Transgenic Mice Is Associated with Adrenocortical Hyperplasia and Enhanced Steroidogenesis Endocrinology, April 1, 1999; 140(4): 1537 - 1543. [Abstract] [Full Text]