دورية أكاديمية
Prostatic intraepithelial neoplasia in mice with conditional disruption of the retinoid X receptor alpha allele in the prostate epithelium.
| العنوان: | Prostatic intraepithelial neoplasia in mice with conditional disruption of the retinoid X receptor alpha allele in the prostate epithelium. |
|---|---|
| المؤلفون: | Huang J; Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA., Powell WC, Khodavirdi AC, Wu J, Makita T, Cardiff RD, Cohen MB, Sucov HM, Roy-Burman P |
| المصدر: | Cancer research [Cancer Res] 2002 Aug 15; Vol. 62 (16), pp. 4812-9. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 2984705R Publication Model: Print Cited Medium: Print ISSN: 0008-5472 (Print) Linking ISSN: 00085472 NLM ISO Abbreviation: Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Baltimore, Md. : American Association for Cancer Research Original Publication: Chicago [etc.] |
| مواضيع طبية MeSH: | Alleles*, Prostatic Intraepithelial Neoplasia/*genetics , Prostatic Neoplasms/*genetics , Receptors, Cell Surface/*genetics , Receptors, Cytoplasmic and Nuclear/*genetics, Animals ; Female ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Integrases/genetics ; Male ; Mice ; Mice, Transgenic ; Mutation ; Prostate/metabolism ; Prostatic Intraepithelial Neoplasia/pathology ; Prostatic Neoplasms/pathology ; Receptors, Melatonin ; Viral Proteins/genetics |
| مستخلص: | Retinoids, which are important regulators of cell growth, differentiation, and apoptosis, have been used in treatment or chemoprevention of multiple cancers including prostate cancer. To elucidate the mechanism of action of retinoids in the context of the prostate, we used the Cre-loxP system to disrupt the retinoid X receptor alpha (RXRalpha) gene specifically in the prostatic epithelium of the mouse. Evidence for tissue-specific gene inactivation was obtained at DNA, RNA, and protein levels. Phenotypic changes in the prostate in the homozygous animals of different age groups ranging from 1 to 15 months were investigated. Developmentally, prostatic ductal branching appeared to be increased from the loss of RXRalpha function. There was also a significant change in the profile of secretory proteins in the RXRalpha mutant prostate relative to littermate controls with intact RXRalpha allele. Histopathologically, homozygous RXRalpha-deficient prostates showed multifocal hyperplasia as early as 4 months of age. Lesions, which could be described as low-grade prostatic intraepithelial neoplasias, were detected after 5 months. Subsequently, beginning at approximately 10 months, high-grade prostatic intraepithelial neoplasias developed in some animals. The incidences of low-grade prostatic intraepithelial neoplasias and high-grade prostatic intraepithelial neoplasias among the animals 10-15 months of age were 62 and 17%, respectively. The heterozygous mutant mice also developed similar prostatic phenotypes but in a delayed manner, implying a role of haploinsufficiency. Together, these results indicated for the first time that a major component of retinoid action in the prostate is mediated by a retinoid receptor, RXRalpha, the inactivation of which in the prostatic epithelium leads to the development of preneoplastic lesions. |
| معلومات مُعتمدة: | R01 CA 59705 United States CA NCI NIH HHS; R21 DK 59192 United States DK NIDDK NIH HHS; T32 CA 09569 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (Receptors, Cell Surface) 0 (Receptors, Cytoplasmic and Nuclear) 0 (Receptors, Melatonin) 0 (Viral Proteins) EC 2.7.7.- (Cre recombinase) EC 2.7.7.- (Integrases) |
| تواريخ الأحداث: | Date Created: 20020817 Date Completed: 20020925 Latest Revision: 20181130 |
| رمز التحديث: | 20240627 |
| PMID: | 12183441 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 0008-5472 |
|---|