Molecular Basis of Posttransplant Squamous Cell Carcinoma: The Potential Role of Cyclosporine A in Carcinogenesis
| Autor: | Hongli Li, Peilin Zhang, Rodney Kovach, Paul van der Sloot, Christopher H. Rassekh, Jeremy Tiu |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Male
medicine.medical_treatment Population Biology medicine.disease_cause Sensitivity and Specificity Immune system Transplantation Immunology Cell Line Tumor Carcinoma medicine Humans education Molecular Biology Oligonucleotide Array Sequence Analysis education.field_of_study Reverse Transcriptase Polymerase Chain Reaction Immunosuppression medicine.disease Squamous carcinoma Gene Expression Regulation Neoplastic Calcineurin Cell Transformation Neoplastic Otorhinolaryngology Epidermoid carcinoma Tissue Transplantation Immunology Carcinoma Squamous Cell Cyclosporine Female Mouth Neoplasms Carcinogenesis Immunosuppressive Agents |
| Zdroj: | The Laryngoscope. 116:762-769 |
| ISSN: | 0023-852X |
| DOI: | 10.1097/01.mlg.0000205170.24517.28 |
| Popis: | Cyclosporine (CSA) is a widely used immunosuppressive agent, predominantly for transplant patients. It is well recognized that transplant patients are prone to develop squamous carcinoma of the skin and mucosa, and this high incidence of squamous carcinoma in the transplant population cannot be explained by immunosuppression alone. We hypothesize that CSA may play a significant role in the transformation of normal epidermal squamous cells to carcinoma. CSA is a specific ligand for calcineurin, a ubiquitously expressed cellular serine/threonine phosphatase, that plays important roles in the immune system and cardiac muscles. Using global gene-profiling methods, we studied the short-time CSA effect on the squamous cell line (SCC-015) using Affymetrix human gene chips (Human U133, 2.0 plus chip). Multiple groups of genes were identified to be responsive to CSA treatment, including many genes of unknown functions. We then used reverse transcriptase-polymerase chain reaction and immunoblot analyses to selectively confirm the results from the chips analyses with emphasis on the regulatory molecules important for cellular functions of apoptosis, DNA damage repair, and cellular transformation. This global gene-profiling study indicated that CSA not only functions as an immunosuppressant on the immune system, but also activates/inhibits a wide array of genes important for cell-cycle regulation, apoptosis, and oncogene/tumor-suppressor activation. These functions of CSA on skin and mucosa systems at the molecular level are likely important in the pathogenesis of squamous carcinoma in transplant patients. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text