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Titolo:
A probasin-large T antigen transgenic mouse line develops prostate adenocarcinoma and neuroendocrine carcinoma with metastatic potential
Autore:
Masumori, N; Thomas, TZ; Chaurand, P; Case, T; Paul, M; Kasper, S; Caprioli, RM; Tsukamoto, T; Shappell, SB; Matusik, RJ;
Indirizzi:
Vanderbilt Univ, Med Ctr, Dept Urol Surg, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 Urol Surg, Nashville, TN 37232 USA Vanderbilt Univ, Med Ctr, Vanderbilt Prostate Canc Ctr, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 Canc Ctr, Nashville, TN 37232 USA Vanderbilt Univ, Med Ctr, Dept Cell Biol, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 Cell Biol, Nashville, TN 37232 USA Vanderbilt Univ, Med Ctr, Mass Spectrometry Res Ctr, Dept Biochem, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 t Biochem, Nashville, TN 37232 USA Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 pt Pathol, Nashville, TN 37232 USA Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 Canc Ctr, Nashville, TN 37232 USA Sapporo Med Univ, Sch Med, Dept Urol Surg & Androl, Sapporo, Hokkaido 060,Japan Sapporo Med Univ Sapporo Hokkaido Japan 060 , Sapporo, Hokkaido 060,Japan
Titolo Testata:
CANCER RESEARCH
fascicolo: 5, volume: 61, anno: 2001,
pagine: 2239 - 2249
SICI:
0008-5472(20010301)61:5<2239:APTATM>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-SUPPRESSOR GENES; NEOPLASTIC HUMAN PROSTATE; ANDROGEN RECEPTOR STATUS; PARACRINE CELL-TYPES; INTRAEPITHELIAL NEOPLASIA; MASS-SPECTROMETRY; MAMMARY ADENOCARCINOMA; MICE; EXPRESSION; CANCER;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
56
Recensione:
Indirizzi per estratti:
Indirizzo: Matusik, RJ Vanderbilt Univ, Med Ctr, Dept Urol Surg, A-1302 Med Ctr N, Nashville, TN 37232 USA Vanderbilt Univ A-1302 Med Ctr N Nashville TN USA 37232 32 USA
Citazione:
N. Masumori et al., "A probasin-large T antigen transgenic mouse line develops prostate adenocarcinoma and neuroendocrine carcinoma with metastatic potential", CANCER RES, 61(5), 2001, pp. 2239-2249

Abstract

Neuroendocrine (NE) cells may be involved not only in growth and differentiation of the normal prostate but also in carcinogenesis and progression ofprostate adenocarcinoma (Pca), including development of androgen resistance. However, the exact pathophysiology; of NE tells in Pca remains poorly understood. Here we describe a transgenic model of Pea with progressive NE differentiation. Seven lines of transgenic mice with the rat prostate-specific large probasin promoter linked to the SV40-large T antigen (Tag) that develop prostatic neoplasia have been established. In this study, one of the seven lines (12T-10) was characterized by examination of 52 mice aged from 2-12 months. With advancing age, low-grade prostatic intraepithelial neoplasia, high-grade prostatic intraepithelial neoplasia, microinvasion, invasivecarcinoma. and poorly or undifferentiated carcinoma with IVE differentiation appeared in the prostates in sequential order. Whereas Tag is expressed uniformly in prostate epithelium, only an increasing subset of cells in prostatic intraepithelial neoplasia showed NE differentiation by chromogranin immunostaining, Frankly invasive carcinoma developing subsequently showed occasional definitive glandular differentiation (adenocarcinoma) and particularly undifferentiated carcinoma with IVE histological features similar to those observed in NE carcinomas in humans. The NE carcinomas occurred in the dorsolateral and ventral lobes and were generally androgen receptor negative. Twenty-one of 32 (66%) mice aged greater than or equal to6 months and 15 of 17 (88%) mice aged greater than or equal to9 months developed metastatic tumors, as confirmed by histology and/or Tag immunohistochemistry. Metastases occurred at the later time points, with metastasis to regional lymphnodes, liver. and lung being particularly common. Metastases showed histological Features of NE differentiation, as confirmed by chromogranin immunostaining and electron microscopy. An athymic nude mouse that received a s.c.implant of a primary NE tumor developed Tag-positive metastatic tumors with similar NE differentiation, Matrix-assisted laser desorption ionization time-of-flight mass spectrometry identified identical protein profiles between the primary NE tumor and lesions in the extraprostatic organs. Hence, inthe 12T-10 large probasin promoter-Tag mouse. high-grade prostatic intraepithelial neoplasia develops progressively greater NE differentiation and progresses to invasive adenocarcinoma and NE carcinoma, with a high percentage of metastases. The predictable progression through these stages will allow testing of therapeutic interventions as well as possible further delineation of the role of NE cells in Pca progression.

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Documento generato il 19/09/20 alle ore 18:45:13