Cell proliferation is insufficient, but loss of tuberin is necessary, for chemically induced nephrocarcinogenicity
| Autor: | Cheryl L. Walker, Serrine S. Lau, Hae Seong Yoon, Terrence J. Monks, Jeffrey I. Everitt |
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| Rok vydání: | 2002 |
| Předmět: |
Male
congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Physiology Urinary system Biology medicine.disease_cause Rats Mutant Strains chemistry.chemical_compound Internal medicine Tuberous Sclerosis Complex 2 Protein Gene expression medicine Animals Cyclin D1 Kidney Hydroquinone Cell growth Tumor Suppressor Proteins Cell cycle medicine.disease Glutathione Kidney Neoplasms Hydroquinones Rats Gene Expression Regulation Neoplastic Repressor Proteins medicine.anatomical_structure Endocrinology chemistry Cancer research Mitogen-Activated Protein Kinases Carcinogenesis Cell Division Kidney disease |
| Zdroj: | American Journal of Physiology-Renal Physiology. 283:F262-F270 |
| ISSN: | 1522-1466 1931-857X |
| DOI: | 10.1152/ajprenal.00261.2001 |
| Popis: | Although 2,3,5-tris-(glutathion- S-yl)hydroquinone (TGHQ; 2.5 μmol/kg ip) markedly increased cell proliferation within the outer stripe of the outer medulla (OSOM) of the kidney in both wild-type ( Tsc2+/+ ) and mutant Eker rats ( Tsc2 EK/+), only TGHQ-treated Tsc2 EK/+ rats developed renal tumors, indicating that cell proliferation per se was not sufficient for tumor development. Tuberin expression was initially induced within the OSOM after TGHQ treatment but was lost within TGHQ-induced renal tumors. High extracellular signal-regulated kinase (ERK) activity occurred in the OSOM of Tsc2 EK/+ rats at 4 mo and in TGHQ-induced renal tumors. Cyclin D1 was also highly expressed in TGHQ-induced renal tumors. Reexpression of Tsc2 in tuberin-negative cells decreased ERK activity, consistent with the growth-suppressive effects of this tumor suppressor gene. Thus 1) stimulation of cell proliferation after toxicant insult is insufficient for tumor formation; 2) tuberin induction after acute tissue injury suggests that Tsc2 is an acute-phase response gene, limiting the proliferative response after injury; and 3) loss of Tsc2 gene function is associated with cell cycle deregulation. |
| Databáze: | OpenAIRE |
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