• Corpus ID: 10063695

Loss of retinoic acid receptors in mouse skin and skin tumors is associated with activation of the ras(Ha) oncogene and high risk for premalignant progression.

  title={Loss of retinoic acid receptors in mouse skin and skin tumors is associated with activation of the ras(Ha) oncogene and high risk for premalignant progression.},
  author={Nadine Darwiche and Giorgio Scita and C S Jones and Susan E. Rutberg and E Greenwald and Tamar Tennenbaum and Steven J. Collins and Luigi M. De Luca and Stuart H. Yuspa},
  journal={Cancer research},
  volume={56 21},
Retinoic acid receptor transcripts (RARalpha and RARgamma) are decreased in benign mouse epidermal tumors relative to normal skin and are almost absent in carcinomas. In this report, the expression of RARalpha and RARgamma proteins was analyzed by immunoblotting in benign skin tumors induced by two different promotion protocols designed to yield tumors at low or high risk for malignant conversion. RARalpha was slightly reduced in papillomas promoted with 12-O-tetradecanoylphorbol-13-acetate… 

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A PMLRARA transgene results in a retinoid-deficient phenotype associated with enhanced susceptibility to skin tumorigenesis.

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Retinoic acid downregulates growth, fibronectin and RARα in 3T3 cells: Ha‐ras blocks this response and RA metabolism

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Mouse skin tumor progression results in differential expression of retinoic acid and retinoid X receptors.

In situ hybridization analysis shows that the two major RAR isoforms, which account for most of RARs in the skin, were expressed in both the basal and suprabasal layers in mouse epidermis, and the increased abundance of transcripts for RXRs and decreased presence of R ARs in skin tumor progression may favor other nuclear signal transduction pathways requiring RXR for heterodimer formation.

Loss of expression of transforming growth factor beta in skin and skin tumors is associated with hyperproliferation and a high risk for malignant conversion.

  • A. GlickA. Kulkarni S. Yuspa
  • Medicine, Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1993
TGF- beta expression and function are compartmentalized in epidermis and epidermal tumors and that loss of TGF-beta is an early, biologically relevant risk factor for malignant progression is shown.

Retinoic acid nuclear receptors and tumor promotion: decreased expression of retinoic acid nuclear receptors by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate.

It is found that TPA downregulates mouse epidermal retinoic acid nuclear receptors (RAR), a superfamily of nuclear steroid/thyroid receptors implicated in mediating effects of retinoics acid (RA), and downregulation of RAR(s) may be an essential component of the mechanism of mouse skin tumor promotion.

Retinoic acid receptors as regulators of human epidermal keratinocyte differentiation.

Results demonstrate that the control of NHEK differentiation by RA is consistent with the interaction of the retinoid with RAR and the regulation of transcription by that ligand-receptor complex.

The Suprabasal Expression of α6β4 Integrin Is Associated with a High Risk for Malignant Progression in Mouse Skin Carcinogenesis

Results indicate that expression of α6β4 integrin in suprabasal strata serves as an early predictive marker to identify benign squamous tumors at high risk for malignant progression.

Detection of mutant Ha-ras genes in chemically initiated mouse skin epidermis before the development of benign tumors.

The hypothesis that initiated epidermal cells containing an activated Ha-ras gene can remain dormant in the skin until a tumor promoter induces regenerative hyperplasia that allows for outgrowth of these cells with an activated ras oncogene to give rise to a benign papilloma is supported.

An activated Harvey ras oncogene produces benign tumours on mouse epidermal tissue

It is shown that when the Ha-MSV v-rasH gene is introduced into cultured keratinocytes by a defective retroviral vector, skin grafts constructed with cells carrying the mutated ras oncogene produce papillomas on athymic nude mouse recipients.

Terminal differentiation in keratinocytes involves positive as well as negative regulation by retinoic acid receptors and retinoid X receptors at retinoid response elements.

A direct and hitherto unrecognized role for RARs and RXRs in positively as well as negatively regulating epidermal differentiation is demonstrated, indicating a novel RAR function independent of the E/F domain.