title: 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.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Christenson
authors.affiliation: Department of Cancer Biology, Beckman Research Institute at City of Hope, 1500 E, Duarte Road, Duarte, CA 91010, USA. skane@coh.org.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Kane
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002460:Cell Line; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D055786:Gene Knockout Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology* / Q000556:secondary; D008321:Mammary Glands, Animal / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism
chemical_list: D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C497929:Ppp1r1b protein, mouse; D020033:Protein Isoforms