Reduced E-cadherin expression contributes to the loss of p27kip1-mediated mechanism of contact inhibition in thyroid anaplastic carcinomas
| Autor: | Angela Celetti, Maria Napolitano, Maria Letizia Motti, Giuseppe Viglietto, Daniela Califano, Francesco Merolla, Floriana Forzati, Barbara Tavernise, Alfredo Fusco, Gustavo Baldassarre |
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| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Cancer Research
TUMOR-CELLS Cell Count Cell Cycle Proteins Cell Communication KeyWords Plus:CELL-ADHESION SYSTEM CPG METHYLATION ALPHA-CATENIN Adenocarcinoma Follicular Thyroid cancer beta Catenin biology Contact Inhibition Retinoblastoma protein EPITHELIAL-CELLS General Medicine CATENIN EXPRESSION Cadherins Cyclin-Dependent Kinases Gene Expression Regulation Neoplastic CDK INHIBITOR Cyclin-Dependent Kinase Inhibitor p27 GROWTH-FACTOR-BETA DEPENDENT KINASE MEDIATED ADHESION medicine.medical_specialty Tumor suppressor gene Cyclin A Cell Line Tumor Cyclins Internal medicine medicine Humans Thyroid Neoplasms Anaplastic carcinoma Cell Proliferation Cell growth Tumor Suppressor Proteins Carcinoma Contact inhibition medicine.disease Carcinoma Papillary Cytoskeletal Proteins Endocrinology Cell culture Cancer cell Trans-Activators Cancer research biology.protein |
| Zdroj: | Carcinogenesis (N.Y., Print) (2005): 733–739. info:cnr-pdr/source/autori:Motti ML, Califano D, Baldassarre G, Celetti A, Merolla F, Forzati F, Napolitano M, Tavernise B, Fusco A, Viglietto G./titolo:Reduced E-cadherin expression contributes to the loss of p27kip1-mediated mechanism of contact inhibition in thyroid anaplastic carcinomas./doi:/rivista:Carcinogenesis (N.Y., Print)/anno:2005/pagina_da:733/pagina_a:739/intervallo_pagine:733–739/volume |
| Popis: | In the present study, we have characterized several human thyroid cancer cell lines of different histotypes for their responsiveness to contact inhibition. We found that cells derived from differentiated carcinoma (TPC-1, WRO) arrest in G(1) phase at confluence, whereas cells derived from anaplastic carcinoma (ARO, FRO and FB1) continue to grow after reaching confluence. Furthermore, we provide experimental evidence that the axis, E-cadherin/beta-catenin/p27(Kip1), represents an integral part of the regulatory mechanism that controls proliferation at a high cell density, whose disruption may play a key role in determining the clinical behaviour of thyroid cancer. This conclusion derives from the finding that: (i) the expression of p27(Kip1) is enhanced at high cell density only in cells responsive to contact inhibition (TPC-1, WRO), but not in contact-inhibition resistant cells (ARO, FRO or FB1 cells); (ii) the increase in p27(Kip1) also resulted in increased levels of p27(Kip1) bound to cyclin E-Cdk2 complex, a reduction in cyclin E-Cdk2 activity and dephosphorylation of the retinoblastoma protein; (iii) antisense inhibition of p27(Kip1) upregulation at high cell density in confluent-sensitive cells completely prevents the confluence-induced growth arrest; (iv) proper expression and/or membrane localization of E-cadherin is observed only in cells responsive to contact inhibition (TPC-1, NPA, WRO) but not in unresponsive cells (ARO, FRO or FB1); (v) disruption of E-cadherin-mediated cell-cell contacts at high cell density induced by an anti-E-cadherin neutralizing antibody, inhibits the induction of p27(kip1) and restores proliferation in contact-inhibited cells; (vi) re-expression of E-cadherin into cells unresponsive to contact inhibition (ARO, FB1) induces a p27(kip1) expression and growth arrest. In summary, our data indicate that the altered response to contact inhibition exhibited by thyroid anaplastic cancer cells is due to the failure to upregulate p27(Kip1) in response to cell-cell interactions. |
| Databáze: | OpenAIRE |
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