SV40 Large T Antigen Expression Driven by col2a1 Regulatory Sequences Immortalizes Articular Chondrocytes but Does Not Allow Stabilization of Type II Collagen Expression - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Experimental Cell Research Année : 1998

SV40 Large T Antigen Expression Driven by col2a1 Regulatory Sequences Immortalizes Articular Chondrocytes but Does Not Allow Stabilization of Type II Collagen Expression

Nathalie Steimberg
  • Fonction : Auteur
Say Viengchareun
Florence Biehlmann
  • Fonction : Auteur
Monique Adolphe
  • Fonction : Auteur
Sophie Thenet
  • Fonction : Auteur

Résumé

Immortalization of chondrocytes by SV40 T Ag has often been reported to trigger the loss of expression of type II collagen, one of the main differentiation markers, although some immortalized chondrocyte lines maintaining a differentiated phenotype have also been described. Here, we show using transient cotransfections in differentiated chondrocytes that, in contrast to c-src, neither SV40 T Ag, nor c-myc, decreases col2a1 transcriptional activity. Then, we report the possibility of immortalizing rabbit articular chondrocytes by expression of SV40 T Ag controlled by the col2a1 promoter and enhancer (pCol2SV). This strategy allows one to select within a population of differentiated chondrocytes those which are able to maintain functional regulation of the col2a1 gene through long-term culture. In precrisis pCol2SV-transfected chondrocytes, all-trans-retinoic acid, a downregulator of col2a1 expression, induced apoptosis, strongly suggesting the strict control of T Ag expression by col2a1 regulatory sequences. Some pCol2SVtransfected chondrocytes were definitively immortalized, after a short crisis period. However, type II collagen synthesis was restricted to a small proportion of cells, which went on to decrease with subculture, while the proportion of cells expressing T Ag was not affected. In these postcrisis cells, T Ag remained at least partially under the control of functional col2a1 regulatory elements as assessed by all-trans-retinoic acid down-regulation.
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hal-03036458 , version 1 (18-12-2020)

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  • HAL Id : hal-03036458 , version 1

Citer

Nathalie Steimberg, Say Viengchareun, Florence Biehlmann, Isabelle Guénal, Bernard Mignotte, et al.. SV40 Large T Antigen Expression Driven by col2a1 Regulatory Sequences Immortalizes Articular Chondrocytes but Does Not Allow Stabilization of Type II Collagen Expression. Experimental Cell Research, 1998, 249, pp.248-259. ⟨hal-03036458⟩

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