| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
From the Department of Pathology* and Division of Cell and Tissue Culture, Kitasato University School of Medicine, Kanagawa; and the Department of Carcinogenesis, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
The functional consequences of up-regulation of ß-catenin as a transcription factor are complex in different tumors. To clarify roles during squamous differentiation (SqD) of endometrial carcinoma (Em Ca) cells, we investigated expression of ß-catenin, as well as cyclin D1, p53, p21WAF1, and PML (promyelocytic leukemia) in 80 cases of Em Ca with SqD areas, in comparison with cell proliferation determined with reference to Ki-67 antigen positivity. The impact of ß-catenin-T-cell factor (TCF)-mediated transcription was also examined using Em Ca cells. In clinical cases, nuclear ß-catenin accumulation was more frequent in SqD areas, being positively linked with expression of cyclin D1, p53, and p21WAF1, and inversely with Ki-67 and PML immunoreactivity. Significant correlations of nuclear ß-catenin, cyclin D1, p53, and p21WAF1 were noted between SqD and the surrounding carcinoma lesions. The Ishikawa cell line, with stable or tetracycline-regulated expression of mutant ß-catenin, showed an increase in expression levels of cyclin D1, p14ARF, p53, and p21WAF1 but not PML, and activation of ß-catenin-TCF4-mediated transcription determined with TOP/FOP constructs. The cell morphology was senescence-like rather than squamoid in appearance. Moreover, overexpressed ß-catenin could activate transcription from p14ARF and cyclin D1 promoters, in a TCF4-dependent manner. These findings indicate that in Em Cas, nuclear ß-catenin can simultaneously induce activation of the p53-p21WAF1 pathway and overexpression of cyclin D1, leading to suppression of cell proliferation or induction of cell senescence. However, overexpression of ß-catenin alone is not sufficient for development of a squamoid phenotype in Em Ca cells, suggesting that nuclear accumulation is an initial signal for trans-differentiation.
This article has been cited by other articles:
 |
|
 |
|
  M. Saegusa, M. Hashimura, T. Kuwata, and I. Okayasu Requirement of the Akt/{beta}-Catenin Pathway for Uterine Carcinosarcoma Genesis, Modulating E-Cadherin Expression Through the Transactivation of Slug Am. J. Pathol., June 1, 2009; 174(6): 2107 - 2115. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Raab, I. Breitkreutz, G. Tonon, J. Zhang, P. J. Hayden, T. Nguyen, J. H. Fruehauf, B. K. Lin, D. Chauhan, T. Hideshima, et al. Targeting PKC: a novel role for beta-catenin in ER stress and apoptotic signaling Blood, February 12, 2009; 113(7): 1513 - 1521. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Moral, C. Segrelles, M. F. Lara, A. B. Martinez-Cruz, C. Lorz, M. Santos, R. Garcia-Escudero, J. Lu, K. Kiguchi, A. Buitrago, et al. Akt Activation Synergizes with Trp53 Loss in Oral Epithelium to Produce a Novel Mouse Model for Head and Neck Squamous Cell Carcinoma Cancer Res., February 1, 2009; 69(3): 1099 - 1108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N Horree, P J van Diest, P van der Groep, D M D S Sie-Go, and A P M Heintz Progressive derailment of cell cycle regulators in endometrial carcinogenesis J. Clin. Pathol., January 1, 2008; 61(1): 36 - 42. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Saegusa, M. Hashimura, T. Kuwata, M. Hamano, Y. Wani, and I. Okayasu A functional role of Cdx2 in {beta}-catenin signaling during transdifferentiation in endometrial carcinomas Carcinogenesis, September 1, 2007; 28(9): 1885 - 1892. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
