+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Ectopic p21sdi1 gene transfer induces retinoic acid receptor beta expression and sensitizes human cancer cells to retinoid treatment

, : Ectopic p21sdi1 gene transfer induces retinoic acid receptor beta expression and sensitizes human cancer cells to retinoid treatment. International Journal of Cancer 103(6): 833-839

The biological effects of retinoic acid (RA) are mediated by nuclear retinoic acid receptors (RARs) that function as ligand-activated transcriptional factors. The response of human cancer cells to RA is known to be associated with the expression of RARbeta. Recent studies have demonstrated that the loss of RARbeta expression is involved in the development of a variety of human malignancies. We show that recombinant adenovirus-mediated p21(sdi1) gene transfer enhances RARbeta mRNA expression as well as protein expression and induces the sensitivity to all-trans RA (ATRA) in human cancer cells. Semi-quantitative reverse transcription-polymerase chain reaction analysis demonstrated that infection with adenovirus carrying human p21(sdi1) gene (Ad5CMV-p21), which encodes a cyclin-dependent kinase inhibitor, induced RARbeta mRNA and protein expression in H1299 human non-small cell lung cancer cells and DLD-1 human colorectal cancer cells. We also found that exogenous introduction of the p21(sdi1) gene transcriptionally activated the upstream promoter function of the RARbeta gene. Treatment with 1 microM of ATRA showed no significant inhibitory effects on the growth of H1299 and DLD-1 cells; after Ad5CMV-p21 infection, however, cells underwent apoptosis with ATRA treatment at the same concentration, suggesting that p21(sdi1) gene transfer sensitized H1299 and DLD-1 cells, presumably, through RARbeta upregulation. We also demonstrated the efficacy of intratumoral injection of Ad5CMV-p21 in combination with systemic administration of ATRA in a nude mice xenograft model. Our results indicate that recombinant adenovirus-mediated p21(sdi1) gene transfer could be potentially useful for the local induction of RA sensitivity in human premalignant and malignant lesions lacking appropriate RARbeta expression.


PMID: 12516107

DOI: 10.1002/ijc.10892

Other references

Imada,, M.Y.shida, T., 1990: Dyeing cellulose. Textile chemist and colorist 22(11): 18-20

Marinella, M.A., 2008: Electrocardiographic changes after shoulder arthroplasty. Hyperkalemia is a commonly encountered electrolyte abnormality in the hospitalized patient population, and can be fatal if not recognized and treated in a timely matter. Although most cases of hyperkalemia in the acute care setting occur in the co...

Baird, S.B., 1990: "A small coalition of antismoking zealots"--look what they did!. Oncology Nursing Forum 17(2): 161-161

Dellweg, H.G.; Sumper, M., 1978: Selective formation of bacterio-opsin trimers by chemical crosslinking of purple membrane. Febs Letters 90(1): 123-126

Rihane, Abdeslam, 2003: Contribution a l'etude du regime alimentaire de la Chouette effraie Tyto alba dans les plaines semi-arides du Maroc atlantique. The diet of Barn Owl Tyto alba was studied from 1999 to 2002 in three areas of Western Morocco. The analysis of 6011 pellets allowed the identification of 12289 preys: 41.3% of which were mammals with a majority of Western, wild Mouse Mus spretus...

Garbarczyk, H., 1989: Proctotrupoid wasps (Hymenoptera: Proctotrupoidea sensu lato) of moist meadows of the Mazovian Lowland. Memorabilia Zoologica, 43: 207-232

Ahmed, F.B.uyan, A.; Shaheen, N.B.rua, S.M.rgetts, B.; Jackson, A., 1991: Effects of socio-demographic conditions on growth of urban school children of Bangladesh. The relationship between socio-demographic variables and growth of 242 school children from five schools in Dhaka city, Bangladesh, was investigated. The socio-demographic data were collected by questionnaire and the anthropometric data were colle...

Bencat, F., 1976: Cultivated tree flora in the Czechoslovakian SSR. Biulleten' 00 47-49

Strettoi E.; Raviola E.; Dacheux R.F., 1989: Synaptic connections of aii amacrine cells in the rabbit retina. Society for Neuroscience Abstracts 15(1): 968

Wauters, O.; Scholtes, F.; Dive, D.; Moonen, G., 2006: Image of the month. A case of rapidly progressing leukoencephalopathy in amyloid angiopathy. Revue Medicale de Liege 61(1): 3-4