Unknown

Dataset Information

0

Darpp-32 and t-Darpp are differentially expressed in normal and malignant mouse mammary tissue.


ABSTRACT:

Background

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.

Methods

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.

Results

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.

Conclusions

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.

SUBMITTER: Christenson JL 

PROVIDER: S-EPMC4147176 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

Darpp-32 and t-Darpp are differentially expressed in normal and malignant mouse mammary tissue.

Christenson Jessica L JL   Kane Susan E SE  

Molecular cancer 20140815


<h4>Background</h4>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 und  ...[more]

Similar Datasets

| S-EPMC6102898 | biostudies-literature
| S-EPMC4951238 | biostudies-literature
| S-EPMC3168893 | biostudies-literature
| S-EPMC5581150 | biostudies-literature
| S-EPMC4573388 | biostudies-literature
| S-EPMC3912167 | biostudies-literature
| S-EPMC7463034 | biostudies-literature
| S-EPMC3399047 | biostudies-literature
| S-EPMC1562452 | biostudies-literature
| S-EPMC1761654 | biostudies-literature