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

Enhanced Expression of the Type II Transforming Growth Factor ß Receptor in Human Pancreatic Cancer Cells without Alteration of Type III Receptor Expression¹

Division of Endocrinology and Metabolism, Departments of Medicine and Biological Chemistry, University of California, Irvine, California 92717 [H. F., Y. Y., M. S. K., R. L. B., M. K.], and Department of Surgery, University of Ulm, D-7900 Ulm, Germany [M. B., H. G. B.]

We have recently found that human pancreatic adenocarcinomas exhibit strong immunostaining for the three mammalian transforming growth factor ß (TGF-ß) isoforms. These important growth-regulating polypeptides bind to a number of proteins, including the type I TGF-ß receptor (TßR-I), type II TGF-ß receptor (TßR-II), and the type III TGF-ß receptor (TßR-III). In the present study we sought to determine whether TßR-II and TßR-III expression is altered in pancreatic cancer. Northern blot analysis indicated that, by comparison with the normal pancreas, pancreatic adenocarcinomas exhibited a 4.6-fold increase (P < 0.01) in mRNA levels encoding TßR-II. In contrast, mRNA levels encoding TßR-III were not increased. In situ hybridization showed that TßR-II mRNA was expressed in the majority of cancer cells, whereas mRNA grains encoding TßR-III were detectable in only a few cancer cells and were present mainly in the surrounding stroma. These findings suggest that enhanced levels of TßR-II may have a role in regulating human pancreatic cancer cell growth, while TßR-III may function in the extracellular matrix.

¹ Supported by USPHS Grant CA40162 awarded by the National Cancer Institute to M. K. and by an award from the Cancer Research Coordinating Committee of the University of California to M. K. and R. L. B. R. L. B. is the recipient of a Bank of America-Giannini Medical Research Fellowship.

² To whom requests for reprints should be addressed, at Division of Endocrinology and Metabolism, Medical Sciences I, C240, University of California, Irvine, CA 92717.

Received 3/15/93. Accepted 5/ 4/93.

This article has been cited by other articles:

				M. Ouaissi, I. Sielezneff, R. Silvestre, B. Sastre, J.-P. Bernard, J. S. Lafontaine, M. J. Payan, L. Dahan, N. Pirro, J. F. Seitz, et al. High Histone Deacetylase 7 (HDAC7) Expression Is Significantly Associated with Adenocarcinomas of the Pancreas Ann. Surg. Oncol., August 1, 2008; 15(8): 2318 - 2328. [Abstract] [Full Text] [PDF]

				K. J. Gordon, M. Dong, E. M. Chislock, T. A. Fields, and G. C. Blobe Loss of type III transforming growth factor {beta} receptor expression increases motility and invasiveness associated with epithelial to mesenchymal transition during pancreatic cancer progression Carcinogenesis, February 1, 2008; 29(2): 252 - 262. [Abstract] [Full Text] [PDF]

				Z. Ji, F. C. Mei, J. Xie, and X. Cheng Oncogenic KRAS Activates Hedgehog Signaling Pathway in Pancreatic Cancer Cells J. Biol. Chem., May 11, 2007; 282(19): 14048 - 14055. [Abstract] [Full Text] [PDF]

				N. B. Arnold, N. Arkus, J. Gunn, and M. Korc The Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid Induces Growth Inhibition and Enhances Gemcitabine-Induced Cell Death in Pancreatic Cancer Clin. Cancer Res., January 1, 2007; 13(1): 18 - 26. [Abstract] [Full Text] [PDF]

				N. Bardeesy, K.-h. Cheng, J. H. Berger, G. C. Chu, J. Pahler, P. Olson, A. F. Hezel, J. Horner, G. Y. Lauwers, D. Hanahan, et al. Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer. Genes & Dev., November 15, 2006; 20(22): 3130 - 3146. [Abstract] [Full Text] [PDF]

				A. F. Hezel, A. C. Kimmelman, B. Z. Stanger, N. Bardeesy, and R. A. DePinho Genetics and biology of pancreatic ductal adenocarcinoma. Genes & Dev., May 15, 2006; 20(10): 1218 - 1249. [Abstract] [Full Text] [PDF]

				J. Li, J. Kleeff, I. Esposito, H. Kayed, K. Felix, T. Giese, M. W. Buchler, and H. Friess Expression Analysis of PMP22/Gas3 in Premalignant and Malignant Pancreatic Lesions J. Histochem. Cytochem., July 1, 2005; 53(7): 885 - 893. [Abstract] [Full Text] [PDF]

				N. Boyer Arnold and M. Korc Smad7 Abrogates Transforming Growth Factor-{beta}1-mediated Growth Inhibition in COLO-357 Cells through Functional Inactivation of the Retinoblastoma Protein J. Biol. Chem., June 10, 2005; 280(23): 21858 - 21866. [Abstract] [Full Text] [PDF]

				G. Subramanian, R. E. Schwarz, L. Higgins, G. McEnroe, S. Chakravarty, S. Dugar, and M. Reiss Targeting Endogenous Transforming Growth Factor {beta} Receptor Signaling in SMAD4-Deficient Human Pancreatic Carcinoma Cells Inhibits Their Invasive Phenotype1 Cancer Res., August 1, 2004; 64(15): 5200 - 5211. [Abstract] [Full Text] [PDF]

				N. B. Arnold, K. Ketterer, J. Kleeff, H. Friess, M. W. Buchler, and M. Korc Thioredoxin Is Downstream of Smad7 in a Pathway That Promotes Growth and Suppresses Cisplatin-Induced Apoptosis in Pancreatic Cancer Cancer Res., May 15, 2004; 64(10): 3599 - 3606. [Abstract] [Full Text] [PDF]

				J Li, J Kleeff, A Guweidhi, I Esposito, P O Berberat, T Giese, M W Buchler, and H Friess RUNX3 expression in primary and metastatic pancreatic cancer J. Clin. Pathol., March 1, 2004; 57(3): 294 - 299. [Abstract] [Full Text] [PDF]

				C. A. Iacobuzio-Donahue, A. Maitra, M. Olsen, A. W. Lowe, N. T. Van Heek, C. Rosty, K. Walter, N. Sato, A. Parker, R. Ashfaq, et al. Exploration of Global Gene Expression Patterns in Pancreatic Adenocarcinoma Using cDNA Microarrays Am. J. Pathol., April 1, 2003; 162(4): 1151 - 1162. [Abstract] [Full Text] [PDF]

				R. L. Baldwin, H. Tran, and B. Y. Karlan Loss of c-myc Repression Coincides with Ovarian Cancer Resistance to Transforming Growth Factor {beta} Growth Arrest Independent of Transforming Growth Factor {beta}/Smad Signaling Cancer Res., March 15, 2003; 63(6): 1413 - 1419. [Abstract] [Full Text] [PDF]

				W.-B. Chen, W. Lenschow, K. Tiede, J. W. Fischer, H. Kalthoff, and H. Ungefroren Smad4/DPC4-dependent Regulation of Biglycan Gene Expression by Transforming Growth Factor-beta in Pancreatic Tumor Cells J. Biol. Chem., September 20, 2002; 277(39): 36118 - 36128. [Abstract] [Full Text] [PDF]

				H. Friess, X.-Z. Guo, A. A. Tempia-Caliera, A. Fukuda, M. E. Martignoni, A. Zimmermann, M. Korc, and M. W. Buchler Differential Expression of Metastasis-Associated Genes in Papilla of Vater and Pancreatic Cancer Correlates With Disease Stage J. Clin. Oncol., May 1, 2001; 19(9): 2422 - 2432. [Abstract] [Full Text] [PDF]

				V. Ellenrieder, S. F. Hendler, W. Boeck, T. Seufferlein, A. Menke, C. Ruhland, G. Adler, and T. M. Gress Transforming Growth Factor {beta}1 Treatment Leads to an Epithelial-Mesenchymal Transdifferentiation of Pancreatic Cancer Cells Requiring Extracellular Signal-regulated Kinase 2 Activation Cancer Res., May 1, 2001; 61(10): 4222 - 4228. [Abstract] [Full Text]

				P. O. Berberat, H. Friess, L. Wang, Z. Zhu, T. Bley, L. Frigeri, A. Zimmermann, and M. W. Büchler Comparative Analysis of Galectins in Primary Tumors and Tumor Metastasis in Human Pancreatic Cancer J. Histochem. Cytochem., April 1, 2001; 49(4): 539 - 549. [Abstract] [Full Text]

				J. Witowski, K. Pawlaczyk, A. Breborowicz, A. Scheuren, M. Kuzlan-Pawlaczyk, J. Wisniewska, A. Polubinska, H. Friess, G. M. Gahl, U. Frei, et al. IL-17 Stimulates Intraperitoneal Neutrophil Infiltration Through the Release of GRO{alpha} Chemokine from Mesothelial Cells J. Immunol., November 15, 2000; 165(10): 5814 - 5821. [Abstract] [Full Text] [PDF]

				T. Cook and R. Urrutia TIEG proteins join the Smads as TGF-beta -regulated transcription factors that control pancreatic cell growth Am J Physiol Gastrointest Liver Physiol, April 1, 2000; 278(4): G513 - G521. [Abstract] [Full Text] [PDF]

				S. J. Miknyoczki, H. Chang, A. Klein-Szanto, C. A. Dionne, and B. A. Ruggeri The Trk Tyrosine Kinase Inhibitor CEP-701 (KT-5555) Exhibits Significant Antitumor Efficacy in Preclinical Xenograft Modelsof Human Pancreatic Ductal Adenocarcinoma Clin. Cancer Res., August 1, 1999; 5(8): 2205 - 2212. [Abstract] [Full Text] [PDF]

				H Friess, Z Lu, H U Graber, A Zimmermann, G Adler, M Korc, R M Schmid, and M W Buchler bax, but not bcl-2, influences the prognosis of human pancreatic cancer Gut, September 1, 1998; 43(3): 414 - 421. [Abstract] [Full Text] [PDF]

				A. Choudhury, R. K. Singh, N. Moniaux, T. H. El-Metwally, J.-P. Aubert, and S. K. Batra Retinoic Acid-dependent Transforming Growth Factor-beta 2-mediated Induction of MUC4 Mucin Expression in Human Pancreatic Tumor Cells Follows Retinoic Acid Receptor-alpha Signaling Pathway J. Biol. Chem., October 20, 2000; 275(43): 33929 - 33936. [Abstract] [Full Text] [PDF]