Darpp-32 and t-Darpp are differentially expressed in normal and malignant mouse mammary tissue.
Darpp-32 and t-Darpp are differentially expressed in normal and malignant mouse mammary tissue.
复制标题
DOI：
10.1186/1476-4598-13-192
复制
发表时间：
2014-08-15
期刊：
影响因子：
37.3
通讯作者：
Kane SE
中科院分区：
文献类型：
--
作者：
Christenson JL;Kane SE
Darpp-32 and t-Darpp are expressed in several forms of breast cancer. Both are transcribed from the gene PPP1R1B via alternative promoters. In humans, Darpp-32 is expressed in both normal and malignant breast tissue, whereas t-Darpp has only been found in malignant breast tissue. The exact biological functions of these proteins in the breast are not known. Although Darpp-32 is a well known regulator of neurotransmission, its role in other tissues and in cancer is less well understood. t-Darpp is known to increase cellular growth, inhibit apoptosis and contribute to acquired drug resistance. The use of transgenic mouse mammary tumor models to study Darpp-32 and t-Darpp in breast cancer in vivo has been limited by a lack of knowledge regarding t-Darpp expression in mice, in both normal and malignant tissue. We used RT-PCR and Western analysis to investigate Darpp-32 and t-Darpp levels in normal and malignant mouse mammary tissue. To determine if Darpp-32 and t-Darpp play a direct role in mammary tumor development, Ppp1r1b gene knockout mice and wild-type mice were crossed with a mouse mammary tumor model. Tumor growth and metastasis were examined. Differences between groups were determined by the two-tailed Student’s t-test. We found that Darpp-32 was expressed in normal mouse mammary tissue and in some breast tumors, whereas t-Darpp was found exclusively in tumors, with t-Darpp usually expressed at equal or higher levels than Darpp-32. Ppp1r1b knockout in MMTV-PyMT transgenic tumor mice resulted in a decrease in tumor growth. The shift in expression from Darpp-32 to t-Darpp during mouse mammary tumorigenesis is reminiscent of the expression patterns observed in humans and is consistent with a role for t-Darpp in promoting cell growth and Darpp-32 in inhibiting cell growth. Decreased tumor growth in Ppp1r1b knockout mice also suggests that t-Darpp plays a direct role, predominant to Darpp-32, in mammary tumor development. These results indicate that transgenic mouse mammary tumor models might be valuable tools for future investigation of Darpp-32 and t-Darpp in breast cancer. The online version of this article (doi:10.1186/1476-4598-13-192) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
3.7
作者：
Gu L;Waliany S;Kane SE
通讯作者：
Kane SE
影响因子：
37.3
作者：
Vangamudi, Bhavatarini;Peng, Dun-Fa;Belkhiri, Abbes
通讯作者：
Belkhiri, Abbes
影响因子：
11.2
作者：
Belkhiri, A;Zaika, A;El-Rifai, W
通讯作者：
El-Rifai, W
影响因子：
11.2
作者：
Hong, Jun;Katsha, Ahmed;El-Rifai, Wael
通讯作者：
El-Rifai, Wael
影响因子：
5.3
作者：
GUY, CT;CARDIFF, RD;MULLER, WJ
通讯作者：
MULLER, WJ