Tumor suppressor PAX6 functions as androgen receptor co-repressor to inhibit prostate cancer growth.
Tumor suppressor PAX6 functions as androgen receptor co-repressor to inhibit prostate cancer growth.
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DOI：
10.1002/pros.21052
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发表时间：
2010-02-01
期刊：
影响因子：
2.8
通讯作者：
Chang, Chawnshang
中科院分区：
文献类型：
--
作者：
Shyr, Chih-Rong;Tsai, Men-Yin;Yeh, Shuyuan;Kang, Hong-Yo;Chang, Yun-Chao;Wong, Pei-Ling;Huang, Chao-Cheng;Huang, Ko-En;Chang, Chawnshang
PAX6是一种转录因子，目前已被认为在胶质母细胞瘤中起肿瘤抑制作用，并作为神经内分泌细胞的早期分化标志物。雄激素受体（AR）在前列腺癌的发生和发展中起着关键作用，因为它的转录活性调节了参与细胞生长、分化和凋亡的基因。为了确定PAX6在前列腺癌中的作用，我们研究了PAX6是否与AR相互作用影响前列腺癌的发展。我们采用免疫染色、RT-PCR和western blotting检测PAX6在前列腺组织和人前列腺癌细胞系中的表达情况。采用MTT法和软琼脂法对过表达PAX6的LNCaP细胞进行细胞生长和集落再生潜力的评价。在前列腺癌组织中，PAX6在正常上皮细胞中的表达高于癌细胞，在LNCaP细胞中的表达低于DU145和PC3细胞，在正常上皮细胞中的表达高于癌细胞。强制表达PAX6抑制LNCaP细胞生长，抑制LNCaP细胞集落形成。pax6与AR相互作用，抑制AR的转录活性。PAX6过表达降低LNCaP细胞雄激素靶基因PSA的表达。在本研究中，我们发现PAX6可能通过与AR相互作用，抑制AR的转录活性和靶基因表达来调节细胞生长和再生，从而起到前列腺癌抑制因子的作用。
PAX6, a transcription factor, has currently been suggested to function as a tumor suppressor in glioblastoma and to act as an early differentiation marker for neuroendocrine cells. The androgen receptor (AR) plays a pivotal role in prostate cancer development and progression due to its transcriptional activity in regulating genes involved in cell growth, differentiation, and apoptosis. To determine the role of PAX6 in prostate cancer, we investigated whether PAX6 interacts with AR to affect prostate cancer development. We used immunostaining, RT-PCR, and western blotting assays to show the expression status of PAX6 in prostate tissue and human prostate cancer cell lines. The role of PAX6 in cell growth and colony regeneration potential of LNCaP cells were evaluated by MTT assay and soft agar assay with PAX6-overexpressed LNCaP cells. Mammalian two-hybrid and coimmunoprecipitation (CoIP) assays were used to demonstrate the interaction between PAX6 and AR. Reporter gene and Q-RT-PCR assays were performed to determine the effects of PAX6 on the function of AR. In prostate cancer tissues, PAX6 expression was stronger in normal epithelial cells than cancer cells, and decreased in LNCaP cells compared to that of DU145 and PC3 cells. Enforced expression of PAX6 suppressed the cell growth of LNCaP cells and also inhibited the colony formation of LNCaP cells. PAX 6 interacted with AR and repressed its transcriptional activity. PAX6 overexpression decreased the expression of androgen target gene PSA in LNCaP cells. In this study, we found that PAX6 may act as a prostate cancer repressor by interacting with AR and repressing the transcriptional activity and target gene expression of AR to regulate cell growth and regeneration.
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影响因子：
--
作者：
MIZOKAMI, A;YEH, SY;CHANG, CS
通讯作者：
CHANG, CS
DOI：
10.1073/pnas.2434383100
发表时间：
2003-12-09
影响因子：
11.1
作者：
Goolsby, J;Marty, MC;Trisler, D
通讯作者：
Trisler, D
影响因子：
3.7
作者：
Bentley, CA;Zidehsarai, MP;Roberts, VJ
通讯作者：
Roberts, VJ
影响因子：
11.2
作者：
Asatiani, E;Huang, WX;Gelmann, EP
通讯作者：
Gelmann, EP
影响因子：
4.8
作者：
COOKE, PS;YOUNG, P;CUNHA, GR
通讯作者：
CUNHA, GR