This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mathieu, M. Articles by Rochefort, H. Search for Related Content PubMed PubMed Citation Articles by Mathieu, M. Articles by Rochefort, H.

Estradiol Down-Regulates the Mannose-6-Phosphate/Insulin-Like Growth Factor-II Receptor Gene and Induces Cathepsin-D in Breast Cancer Cells: A Receptor Saturation Mechanism to Increase the Secretion of Lysosomal Proenzymes

Unité Hormones et Cancer (U 148) 34090 Montpellier, France

Address requests for reprints to: Dr. Henri Rochefort, INSERM U 148, Unit Hormones and Cancer, 60 rue de Navacelles, 34090 Montpellier, France.

Abstract

We have studied the regulation by estradiol of the mannose-6-phosphate (Man-6-P)/insulin-like growth factor-II (IGF-II) receptor concentration in different breast cancer cell lines. The mRNA level was assayed by Northern blot using the H5.1 cDNA probe. The protein level was assayed by Western ligand blot, by binding saturation with [¹²⁵I]procathepsin-D on total membrane preparations, and by immunoprecipitation of ³⁵S-labeled proteins. In three estrogen receptor-positive cell lines (MCF7, T47D, and ZR75-1), estradiol specifically decreased the steady state level of the Man-6-P/IGF-II receptor protein and mRNA. Moreover, in different cell lines and in primary culture of normal mammary cells, the secretion of procathepsin-D was inversely correlated with the level of Man-6-P/IGF-II receptor protein and mRNA.

We conclude that estradiol down-regulates the Man-6-P/IGF-II receptor in breast cancer cells. Since two of its ligands, procathepsin-D and IGF-II, are induced by estrogen, we propose that the Man-6-P/IGF-II receptor becomes saturated after estrogen treatment. This model might explain the previously described estrogen-induced secretion of procathepsin-D and other lysosomal proenzymes routed by the same transport system.

FOOTNOTES

This work was supported by the Institut National de la Santé et de la Recherche Médicale, the Faculty of Medicine of Montpellier, the Association pour la Recherche sur le Cancer, and the Ministère de la Recherche et de I'Enseignement Superieur (fellowship to M.M.).

Received for publication April 9, 1990. Revision received February 3, 1991. Accepted for publication March 8, 1991.

This article has been cited by other articles:

				N. Matsumoto, O. D. Jo, R. N. J. Shih, E. J. Brochmann, S. S. Murray, V. Hong, J. Yanagawa, and N. Yanagawa Increased cathepsin D release by Hyp mouse osteoblast cells Am J Physiol Endocrinol Metab, July 1, 2005; 289(1): E123 - E132. [Abstract] [Full Text] [PDF]

				H. Yu, X.-O. Shu, B. D. L. Li, Q. Dai, Y.-T. Gao, F. Jin, and W. Zheng Joint Effect of Insulin-like Growth Factors and Sex Steroids on Breast Cancer Risk Cancer Epidemiol. Biomarkers Prev., October 1, 2003; 12(10): 1067 - 1073. [Abstract] [Full Text] [PDF]

				S. Oesterreich, P. Zhang, R. L. Guler, X. Sun, E. M. Curran, W. V. Welshons, C. K. Osborne, and A. V. Lee Re-expression of Estrogen Receptor {alpha} in Estrogen Receptor {alpha}-negative MCF-7 Cells Restores both Estrogen and Insulin-like Growth Factor-mediated Signaling and Growth Cancer Res., August 1, 2001; 61(15): 5771 - 5777. [Abstract] [Full Text] [PDF]

				H. Yu and T. Rohan Role of the Insulin-Like Growth Factor Family in Cancer Development and Progression J Natl Cancer Inst, September 20, 2000; 92(18): 1472 - 1489. [Abstract] [Full Text] [PDF]

				A. V. Lee, J. G. Jackson, J. L. Gooch, S. G. Hilsenbeck, E. Coronado-Heinsohn, C. K. Osborne, and D. Yee Enhancement of Insulin-Like Growth Factor Signaling in Human Breast Cancer: Estrogen Regulation of Insulin Receptor Substrate-1 Expression in Vitro and in Vivo Mol. Endocrinol., May 1, 1999; 13(5): 787 - 796. [Abstract] [Full Text]

				V Laurent-Matha, M. Farnoud, A Lucas, C Rougeot, M Garcia, and H Rochefort Endocytosis of pro-cathepsin D into breast cancer cells is mostly independent of mannose-6-phosphate receptors J. Cell Sci., January 9, 1998; 111(17): 2539 - 2549. [Abstract] [PDF]

				H. Munier-Lehmann, F. Mauxion, U. Bauer, P. Lobel, and B. Hoflack Re-expression of the Mannose 6-Phosphate Receptors in Receptor-deficient Fibroblasts. COMPLEMENTARY FUNCTION OF THE TWO MANNOSE 6-PHOSPHATE RECEPTORS IN LYSOSOMAL ENZYME TARGETING J. Biol. Chem., June 21, 1996; 271(25): 15166 - 15174. [Abstract] [Full Text] [PDF]

				S. Fortenberry, J. Schorey, and J. Chirgwin Role of glycosylation in the expression of human procathepsin D J. Cell Sci., January 5, 1995; 108(5): 2001 - 2006. [Abstract] [PDF]

				J. Schorey, S. Fortenberry, and J. Chirgwin Lysine residues in the C-terminal lobe and lysosomal targeting of procathepsin D J. Cell Sci., January 5, 1995; 108(5): 2007 - 2015. [Abstract] [PDF]

				J. C. Byrd and R. G. MacDonald Mechanisms for High Affinity Mannose 6-Phosphate Ligand Binding to the Insulin-like Growth Factor II/Mannose 6-Phosphate Receptor. NEGATIVE COOPERATIVITY AND RECEPTOR OLIGOMERIZATION J. Biol. Chem., June 16, 2000; 275(25): 18638 - 18646. [Abstract] [Full Text] [PDF]

				K. J. Scheidegger, B. Cenni, D. Picard, and P. Delafontaine Estradiol Decreases IGF-1 and IGF-1 Receptor Expression in Rat Aortic Smooth Muscle Cells. MECHANISMS FOR ITS ATHEROPROTECTIVE EFFECTS J. Biol. Chem., December 1, 2000; 275(49): 38921 - 38928. [Abstract] [Full Text] [PDF]