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.

@article{Darwiche1996LossOR,
  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},
  year={1996},
  volume={56 21},
  pages={
          4942-9
        }
}
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… Expand
Overexpression of retinoic acid receptors alpha and gamma into neoplastic epidermal cells causes retinoic acid-induced growth arrest and apoptosis.
TLDR
The results suggest that RARalpha and RARgamma enhance growth suppression and apoptosis of neoplastic epidermal keratinocytes through distinct as well as overlapping mechanisms of cell cycle control. Expand
Malignant transformation of DMBA/TPA-induced papillomas and nevi in the skin of mice selectively lacking retinoid-X-receptor alpha in epidermal keratinocytes.
TLDR
Distinct RXRalpha-mediated molecular events appear to be involved, in keratinocytes, in cell-aut autonomous suppression of epidermal tumorigenesis and malignant progression, and in non-cell-autonomous suppression of nevi formation and progression. Expand
Topical retinoic acid reduces skin papilloma formation but resistant papillomas are at high risk for malignant conversion.
TLDR
Examination of tumor markers at weeks 14 and 22 of the tumor-induction experiments in vivo indicated that papillomas evolving during RA treatment exhibited a phenotype of high progression risk, even in the TPA-promoted groups, but papilloma resistant to RA may have altered TGF-beta signaling and progress to carcinomas at an increased frequency. Expand
Immunofluorescence localization of nuclear retinoid receptors in psoriasis versus normal human skin.
TLDR
The results support the idea that psoriasis is associated with abnormal retinoid signalling in lesional epidermis and that mRNA expression of RARalpha and RXRalpha is down-regulated in psoriatic lesions as compared with non-lesional human skin. Expand
Expression of nuclear retinoid receptors in normal, premalignant and malignant gastric tissues determined by in situ hybridization
TLDR
Investigation of expression of retinoic acid receptors and retinoid x receptors in premalignant and malignant formalin-fixed paraffin-embedded gastric tissues suggests a significant role of RARα during gastric carcinogenesis, and normal gastric mucosa expressed both RARs and RXRs, which supports the physiological role of retINOic acid on normal gastrics mucosa. Expand
Involvement of all-trans-retinoic acid in the breakdown of retinoic acid receptors α and γ through proteasomes in mcf-7 human breast cancer cells
TLDR
The data suggest that RA induces the breakdown of RARs through a process involving ubiquitination and that this phenomenon causes a reduction in the formation of DNA-receptor complexes. Expand
Pharmacologic retinoid signaling and physiologic retinoic acid receptor signaling inhibit basal cell carcinoma tumorigenesis
TLDR
It was found that BCCs did not reappear for at least 5 months after topical drug treatment was stopped and that already developed, microscopic BCCs were susceptible to tazarotene inhibition, suggesting that endogenous RAR signaling restrains BCC growth. Expand
A PMLRARA transgene results in a retinoid-deficient phenotype associated with enhanced susceptibility to skin tumorigenesis.
TLDR
Results suggest that local interruption of PML and RARalpha signaling in the skin, together with a systemic retinoid deficiency, initiates a tumor induction pathway that is independent of ras activation. Expand
Low synthesis of retinoic acid due to impaired cytochrome P450 1a1 expression in mouse xeroderma pigmentosum fibroblasts.
New tumor formation was suppressed by retinoic acid (RA) administration in xeroderma pigmentosum (XP) patients who have a defect in nuclear excision repair. However, the inhibition is not due toExpand
Maintenance of retinoic acid receptor alpha pools by granulocyte colony-stimulating factor and lithium chloride in all-trans retinoic acid-treated WEHI-3B leukemia cells: relevance to the synergistic induction of terminal differentiation.
TLDR
It was found that steady-state retinoic acid receptor alpha (RARalpha) protein levels were markedly reduced in these cells after exposure to ATRA, suggesting that the prevention of RARalpha protein loss by G-CSF or LiCl in ATRA-treated cells functioned to extend the differentiation response to the retinoid. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 59 REFERENCES
Mouse skin tumor progression results in differential expression of retinoic acid and retinoid X receptors.
TLDR
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. Expand
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. Glick, A. Kulkarni, +6 authors S. Yuspa
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1993
TLDR
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. Expand
Retinoic acid nuclear receptors and tumor promotion: decreased expression of retinoic acid nuclear receptors by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate.
TLDR
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. Expand
Retinoic acid receptors as regulators of human epidermal keratinocyte differentiation.
TLDR
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. Expand
The Suprabasal Expression of α6β4 Integrin Is Associated with a High Risk for Malignant Progression in Mouse Skin Carcinogenesis
TLDR
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. Expand
Dominant negative retinoid X receptor beta inhibits retinoic acid-responsive gene regulation in embryonal carcinoma cells.
TLDR
It is shown that in F9 EC cells expression of DBD- leads to inhibition of the growth arrest that accompanies RA-induced differentiation, demonstrating that RXR beta and partner receptors play a central role in RA-mediated gene regulation and in the control of growth and differentiation in EC cells. Expand
Detection of mutant Ha-ras genes in chemically initiated mouse skin epidermis before the development of benign tumors.
TLDR
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. Expand
An activated Harvey ras oncogene produces benign tumours on mouse epidermal tissue
TLDR
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. Expand
c-fos is required for malignant progression of skin tumors
TLDR
Experiments in which v-H-ras-expressing keratinocytes were grafted onto nude mice suggest that c-fos-deficient cells have an intrinsic defect that hinders tumorigenesis. Expand
Terminal differentiation in keratinocytes involves positive as well as negative regulation by retinoic acid receptors and retinoid X receptors at retinoid response elements.
TLDR
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. Expand
...
1
2
3
4
5
...