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Titolo:
Sex hormone-induced carcinogenesis in Rb-deficient prostate tissue
Autore:
Wang, YH; Hayward, SW; Donjacour, AA; Young, P; Jacks, T; Sage, J; Dahiya, R; Cardiff, RD; Day, ML; Cunha, GR;
Indirizzi:
Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA MIT, Ctr Canc Res, Howard Hughes Med Inst, Cambridge, MA 02139 USA MIT Cambridge MA USA 02139 oward Hughes Med Inst, Cambridge, MA 02139 USA MIT, Dept Biol, Cambridge, MA 02139 USA MIT Cambridge MA USA 02139MIT, Dept Biol, Cambridge, MA 02139 USA Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA Univ Calif Davis Davis CA USA 95616 Ctr Comparat Med, Davis, CA 95616 USA Univ Michigan, Dept Surg, Ctr Comprehens Canc, Div Urol, Ann Arbor, MI 48109 USA Univ Michigan Ann Arbor MI USA 48109 c, Div Urol, Ann Arbor, MI 48109 USA
Titolo Testata:
CANCER RESEARCH
fascicolo: 21, volume: 60, anno: 2000,
pagine: 6008 - 6017
SICI:
0008-5472(20001101)60:21<6008:SHCIRP>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
RETINOBLASTOMA SUSCEPTIBILITY GENE; ANDROGEN RECEPTOR EXPRESSION; NEONATAL ESTROGEN EXPOSURE; HUMAN-BREAST-CANCER; MOLECULE E-CADHERIN; LOBUND-WISTAR RATS; CELL-CYCLE CONTROL; EPITHELIAL INTERACTIONS; REPRODUCTIVE-TRACT; NOBLE RATS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
95
Recensione:
Indirizzi per estratti:
Indirizzo: Cunha, GR Univ Calif San Francisco, Dept Anat, Box 0452, San Francisco, CA94143 USA Univ Calif San Francisco Box 0452 San Francisco CA USA 94143 USA
Citazione:
Y.H. Wang et al., "Sex hormone-induced carcinogenesis in Rb-deficient prostate tissue", CANCER RES, 60(21), 2000, pp. 6008-6017

Abstract

The retinoblastoma (Rb) gene product is a prototypic tumor suppressor. Mice lacking the Rb gene are not viable and die in utero at similar to 13 daysof gestation. In this study, me have rescued Rb-/- prostates by grafting pelvic organ rudiments from Rb-/- mouse embryos under the renal capsule of adult male nude mouse hosts. Grafts of embryonic pelvic organs developed into functional prostatic tissue. Some of the prostatic tissue generated was further used to construct chimeric prostatic tissue recombinants by combining wild-type rat urogenital mesenchyme (rUGM) with Rb-/- and Rb+/+ prostaticepithelium (PRE). The tissue recombinants were grown as subcapsular renal grafts and treated from the time of grafting with Silastic capsules containing 25 mg of testosterone plus 2.5 mg of estradiol, During 5-8 weeks of hormone treatment, rUGM+Rb+/+PRE, tissue recombinants developed prostatic hyperplasia, whereas PRE in rUGM(+)Rb(-/-)PRE tissue recombinants developed hyperplasia, atypical hyperplasia, and carcinoma. During carcinogenesis in rUGM+Rb-/-PRE tissue recombinants, prostatic epithelial cells of the basal lineage disappeared, whereas the luminal cells underwent carcinogenesis, Epithelial E-cadherin almost totally disappeared. In all cases, epithelial PCNA labeling was elevated in tissue recombinants containing Rb-/- versus Rb+/+ epithelium, These epithelial changes were associated with almost total lossof smooth muscle cells in the stroma, In contrast, in untreated hosts rUGMRb+/+PRE tissue recombinants developed normally, and rUGM+Rb-/-PRE tissue recombinants developed mild epithelial hyperplasia, The results of this study demonstrate that Rb-/- prostatic tissue can be rescued from embryonic Lethal mice and used to test its susceptibility to hormonal carcinogenesis. Deletion of the Rb gene predisposes prostatic epithelium to hyperplasia and increases proliferative activity. Susceptibility to hormonal carcinogenesisin response to exogenous testosterone + estradiol is manifested in the progression from atypical hyperplasia to carcinoma. Thus, these findings demonstrate that the absence of the Rb tumor suppressor gene may predispose prostatic epithelial cells to carcinogenesis. Rescue of organs from Rb-/- embryos not only provides an opportunity to analyze the Rb gene pathway in the development and progression of prostate cancer but also provides an opportunity for specifically evaluating the role of the Rb pathway in development and carcinogenesis in other organs, such as the mammary gland and colon. Because rUGM greatly stimulates prostatic epithelial proliferation, the tissuerecombinant model is a particularly useful toot for assessing the functional role of other genes in prostatic carcinogenesis through use of the appropriate transgenic or gene knockout mice.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/07/20 alle ore 03:59:08