This Article Full Text 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 Muro-Cacho, C. A. Articles by Muñoz-Antonia, T. Search for Related Content PubMed PubMed Citation Articles by Muro-Cacho, C. A. Articles by Muñoz-Antonia, T.

Defective Transforming Growth Factor ß Signaling Pathway in Head and Neck Squamous Cell Carcinoma as Evidenced by the Lack of Expression of Activated Smad2¹

Interdisciplinary Oncology Program, H. Lee Moffitt Cancer Center and Research Institute [C. A. M-C., T. M-A.] and Department of Pathology [C. A. M-C., S. L.], University of South Florida, Tampa, Florida 33612, and Department of Pharmacology and The Puerto Rico Cancer Center, University of Puerto Rico, Rio Piedras, Puerto Rico 00936 [K. R-O.]

Purpose: Transforming growth factor ß (TGF-ß) regulates cell growth and differentiation, in normal squamous epithelium, via specific TGF-ß receptors and intracellular signaling molecules (Smads). We have previously observed that TGF-ß type II receptor (TßR-II) expression decreases in squamous cell carcinomas as tumors become less differentiated and more biologically aggressive. However, a small fraction of tumors remain TßR-II positive. In this article, we examine the integrity of the other members of the TGF-ß-signaling machinery, the Smad proteins.

Experimental Design: Thirteen archived head and neck squamous cell carcinomas were selected from the files of the Pathology Department of the H. Lee Moffitt Cancer Center. Protein immunoexpression was quantitated by image analysis in the context of histopathological parameters. Mutation analysis of the MADR2/Smad2 gene was also performed.

Results: In both TßR-II-positive and TßR-II-negative tumors, expression of the non-TGF-ß-specific Smads (4, 6, and 7) was variable, whereas expression of the pathway-specific Smad2 was lost in 38% of the tumors. Expression of the activated, phosphorylated form of this molecule, Smad2-P, was lost in approximately 70% of the tumors. No abnormal mRNA expression and no mutations in the MADR2/Smad2 gene were observed.

Conclusions: These results suggest that multiple defects in TGF-ß signaling, both at the receptor and postreceptor level, may play a role in the oncogenesis of head and neck squamous cell carcinoma.

This article has been cited by other articles:

				W. M. Grady Transforming Growth Factor-{beta}, Smads, and Cancer Clin. Cancer Res., May 1, 2005; 11(9): 3151 - 3154. [Full Text] [PDF]

				A. Baez, A. Cantor, S. Fonseca, M. Marcos-Martinez, L. A. Mathews, C. A. Muro-Cacho, and T. Munoz-Antonia Differences in Smad4 Expression in Human Papillomavirus Type 16-Positive and Human Papillomavirus Type 16-Negative Head and Neck Squamous Cell Carcinoma Clin. Cancer Res., May 1, 2005; 11(9): 3191 - 3197. [Abstract] [Full Text] [PDF]

				S.S. Prime, M. Davies, M. Pring, and I.C. Paterson THE ROLE OF TGF-{beta} IN EPITHELIAL MALIGNANCY AND ITS RELEVANCE TO THE PATHOGENESIS OF ORAL CANCER (PART II) Crit. Rev. Oral. Biol. Med., November 1, 2004; 15(6): 337 - 347. [Abstract] [Full Text] [PDF]

				T. T. Maliekal, R. J. Anto, and D. Karunagaran Differential Activation of Smads in HeLa and SiHa Cells That Differ in Their Response to Transforming Growth Factor-{beta} J. Biol. Chem., August 27, 2004; 279(35): 36287 - 36292. [Abstract] [Full Text] [PDF]

				S. H. Tannehill-Gregg, D. F. Kusewitt, T. J. Rosol, and M. Weinstein The Roles of Smad2 and Smad3 in the Development of Chemically Induced Skin Tumors in Mice Vet. Pathol., May 1, 2004; 41(3): 278 - 282. [Abstract] [Full Text] [PDF]

				F. Tian, S. DaCosta Byfield, W. T. Parks, S. Yoo, A. Felici, B. Tang, E. Piek, L. M. Wakefield, and A. B. Roberts Reduction in Smad2/3 Signaling Enhances Tumorigenesis but Suppresses Metastasis of Breast Cancer Cell Lines Cancer Res., December 1, 2003; 63(23): 8284 - 8292. [Abstract] [Full Text] [PDF]

				F. Beuschlein, B. D. Looyenga, S. E. Bleasdale, C. Mutch, D. L. Bavers, A. F. Parlow, J. H. Nilson, and G. D. Hammer Activin Induces x-Zone Apoptosis That Inhibits Luteinizing Hormone-Dependent Adrenocortical Tumor Formation in Inhibin-Deficient Mice Mol. Cell. Biol., June 1, 2003; 23(11): 3951 - 3964. [Abstract] [Full Text] [PDF]

				R. L. Ferris and W. M. Koch Connective Tissue Disease Coincident With Nasopharyngeal Carcinoma: Two Sporadic Cases in a Western Population Arch Otolaryngol Head Neck Surg, January 1, 2003; 129(1): 101 - 105. [Abstract] [Full Text] [PDF]

				M. Fukuchi, Y. Fukai, N. Masuda, T. Miyazaki, M. Nakajima, M. Sohda, R. Manda, K. Tsukada, H. Kato, and H. Kuwano High-Level Expression of the Smad Ubiquitin Ligase Smurf2 Correlates with Poor Prognosis in Patients with Esophageal Squamous Cell Carcinoma Cancer Res., December 15, 2002; 62(24): 7162 - 7165. [Abstract] [Full Text] [PDF]

				K. B. Glaser, J. Li, M. E. Aakre, D. W. Morgan, G. Sheppard, K. D. Stewart, J. Pollock, P. Lee, C. Z. O'Connor, S. N. Anderson, et al. Transforming Growth Factor {beta} Mimetics: Discovery of 7-[4-(4-Cyanophenyl)phenoxy]-Heptanohydroxamic Acid, a Biaryl Hydroxamate Inhibitor of Histone Deacetylase Mol. Cancer Ther., August 1, 2002; 1(10): 759 - 768. [Abstract] [Full Text] [PDF]

				J. Adnane, C. Muro-Cacho, L. Mathews, S. M. Sebti, and T. Munoz-Antonia Suppression of Rho B Expression in Invasive Carcinoma from Head and Neck Cancer Patients Clin. Cancer Res., July 1, 2002; 8(7): 2225 - 2232. [Abstract] [Full Text] [PDF]