Expression of a Y-located human proto-oncogene TSPY in a transgenic mouse model of prostate cancer.
Expression of a Y-located human proto-oncogene TSPY in a transgenic mouse model of prostate cancer.
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DOI：
10.1186/2045-3701-4-9
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发表时间：
2014-02-17
影响因子：
7.5
通讯作者：
Lau YF
中科院分区：
文献类型：
--
作者：
Kido T;Schubert S;Hatakeyama S;Ohyama C;Schmidtke J;Lau YF
人TSPY是Y染色体上性腺母细胞瘤基因座（GBY）的推定基因。各种分子、病理学和转基因小鼠研究表明，TSPY是一种Y定位的原癌基因，有助于人类癌症的起始/进展，包括生殖细胞肿瘤和各种体细胞癌症，如前列腺癌和肝癌以及黑色素瘤。TgTSPY 9转基因小鼠系含有8.2-kb的人TSPY结构基因，该基因串联整合在小鼠Y染色体中，并以与人基因组中的内源基因相似的模式表达。这种人类TSPY基因的小鼠模型提供了一个机会，以检查其在各种人类疾病（如人类癌症）小鼠模型中的行为和潜在贡献。我们研究了这种TSPY转基因在LADY小鼠前列腺癌模型中的表达，该模型携带由大鼠probasin启动子指导的SV 40 T抗原基因;并将表达模式与人类前列腺癌标本中内源性TSPY基因和生物标志物的表达模式进行了比较。通过将Y定位的TSPY转基因引入LADY小鼠，我们已经在该前列腺癌小鼠模型中检查了人TSPY在前列腺肿瘤发生期间的表达模式。我们的研究结果表明，TSPY转基因被激活在选定地区的细胞过多的基质，但不是在上皮内细胞/肿瘤的TgTSPY 9/LADY小鼠前列腺。使用上皮细胞的特异性生物标志物FOXA 1，我们证明了在肿瘤发生的晚期阶段，TSPY阳性细胞仅在LADY模型中的癌性间质中增殖。相比之下，在人类情况下，TSPY主要与PIN病变的上皮细胞中的FOXA 1以及各种恶性程度的临床前列腺癌样品中的腺癌细胞中的FOXA 1和另一种癌症生物标志物AMACR共表达。我们的数据表明，人TSPY可以在前列腺肿瘤发生过程中异常激活，并可能有助于前列腺癌的异质性。LADY小鼠模型和临床前列腺癌之间的人TSPY的差异表达模式表明，目前的小鼠模型用于研究TSPY在疾病状态下的行为或前列腺癌发展的潜在局限性。
The human TSPY is the putative gene for the gonadoblastoma locus on the Y chromosome (GBY). Various molecular, pathological and transgenic mouse studies suggest that TSPY is a Y-located proto-oncogene contributing to the initiation/progression in human cancers, including germ cell tumors and various somatic cancers, such as prostate and liver cancer, and melanoma. The TgTSPY9 transgenic mouse line harbors a 8.2-kb human TSPY structural gene, which is tandemly integrated in the mouse Y chromosome, and expressed in a similar pattern as that of the endogenous gene in the human genome. This mouse model of human TSPY gene offers an opportunity to examine its behavior and potential contribution in various mouse models of human diseases, such as human cancers. We had investigated the expression of such TSPY-transgene in the LADY mouse model of prostate cancer, harboring a SV40 T antigen gene directed by a rat probasin promoter; and compared the expression pattern with those of endogenous TSPY gene and biomarkers in human prostate cancer specimens. By introducing the Y-located TSPY-transgene to the LADY mice, we had examined the expression pattern of the human TSPY during prostatic oncogenesis in this mouse model of prostate cancer. Our results showed that the TSPY-transgene was activated in selected areas of the hypercellular stroma but not in the intraepithelial cells/neoplasia in the prostates of TgTSPY9/LADY mice. Using a specific biomarker, FOXA1, for epithelial cells, we demonstrated that TSPY-positive cells proliferated exclusively in the cancerous stroma in the LADY model at late stages of tumorigenesis. In contrast, in the human situation, TSPY was predominantly co-expressed with FOXA1 in the epithelial cells of PIN lesions and FOXA1 and another cancer biomarker, AMACR, in the adenocarcinoma cells in clinical prostate cancer samples of various degrees of malignancy. Our data show that human TSPY could be abnormally activated during prostatic oncogenesis, and could possibly contribute to the heterogeneity of prostate cancer. The differential expression patterns of the human TSPY between the LADY mouse model and clinical prostate cancer suggest potential limitations of current mouse models for studies of either TSPY behavior in diseased conditions or prostate cancer development.
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影响因子：
5.9
作者：
Kido, Tatsuo;Schubert, Stephanie;Lau, Yun-Fai Chris
通讯作者：
Lau, Yun-Fai Chris
影响因子：
6.4
作者：
Kido, Tatsuo;Lau, Yun-Fai Chris
通讯作者：
Lau, Yun-Fai Chris
影响因子：
4.7
作者：
Gallagher, WM;Bergin, OE;Easty, DJ
通讯作者：
Easty, DJ
影响因子：
1.7
作者：
Lau, YFC;Lau, HW;Kömüves, LG
通讯作者：
Kömüves, LG
DOI：
10.1159/000056838
发表时间：
2000-01-01
期刊：
CYTOGENETICS AND CELL GENETICS
影响因子：
--
作者：
Lau, YFC;Chou, PM;Kömüves, LG
通讯作者：
Kömüves, LG