Progression of prostatic intraepithelial neoplasia to invasive carcinoma in C3(1)/SV40 large T antigen transgenic mice: histopathological and molecular biological alterations.
Progression of prostatic intraepithelial neoplasia to invasive carcinoma in C3(1)/SV40 large T antigen transgenic mice: histopathological and molecular biological alterations.
复制标题
C3(1)/SV40 大 T 抗原转基因小鼠前列腺上皮内瘤变进展为浸润性癌：组织病理学和分子生物学改变。
作者：
M. Shibata;J. Ward;D. Devor;M. L. Liu;J. Green
The progression of prostatic intraepithelial neoplasia (PIN) to invasive prostate carcinoma has been analyzed in the C3(1)/T(AG) transgenic mouse model and appears very similar to the process proposed to occur in humans. PIN lesions in these transgenic mice histologically resemble those found in human PIN. Low-grade PIN was observed in the ventral and dorsolateral lobes at 2 months of age, whereas high-grade PIN was found in both lobes by 5 months of age. A progressive increase in the number of PIN lesions was observed with age. Prostate carcinomas, which appeared to arise from PIN lesions, were found by 7 months of age in the ventral lobe and 11 months of age in the dorsolateral lobe. Expression of T(AG) mRNA and protein in these lesions correlated with the development of PIN and carcinomas, as did the overexpression of p53 protein. Apoptosis levels were quite low in normal epithelial cells, moderate in low-grade PIN, and high in high-grade PIN and carcinomas. Levels of expression of proliferating cell nuclear antigen correlated with the degree of severity of the prostate lesions. Eighteen % of PIN lesions were found to already harbor Ha-ras mutations, whereas 33% of carcinomas showed various mutations in Ha-ras, Ki-ras, and/or p53. Mutations in Ha-ras may, therefore, be an early event in a significant portion of PIN lesions. Because high-grade PIN showed many characteristics similar to those observed in carcinomas and high-grade PIN was often found contiguous to carcinomas, we conclude that high-grade PIN is a precursor lesion of prostate carcinoma in this transgenic model. These transgenic mice will be useful to study mechanisms responsible for the progression of invasive carcinomas from PIN precursor lesions, as may occur during the development of prostate cancer in humans.
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DOI：
10.1073/pnas.87.22.8751
发表时间：
1990-11-01
影响因子：
11.1
作者：
CARTER, BS;EWING, CM;ISAACS, WB
通讯作者：
ISAACS, WB
前列腺癌细胞增殖和凋亡——与病理分期的相关性？
DOI：
--
发表时间：
1996
期刊：
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.
影响因子：
--
作者：
Brown,C;Sauvageot,J;Kahane,H;Epstein,JI
通讯作者：
Epstein,JI
通过荧光原位杂交检测到的 7 号染色体的非整倍性和异型性是前列腺癌预后不良的标志。
影响因子：
11.2
作者：
Alcaraz,A;Takahashi,S;Brown,JA;Herath,JF;Bergstralh,EJ;Larson-Keller,JJ;Lieber,MM;Jenkins,RB
通讯作者：
Jenkins,RB
影响因子：
11.2
作者：
B. Carter;J. I. Epstein;W. Isaacs
通讯作者：
B. Carter;J. I. Epstein;W. Isaacs
影响因子：
11.2
作者：
J. Qian;D. Bostwick;Satoru Takahashi;T. Borell;J. Herath;M. Lieber;Robert B. Jenkins
通讯作者：
J. Qian;D. Bostwick;Satoru Takahashi;T. Borell;J. Herath;M. Lieber;Robert B. Jenkins