Accession Number : ADA554208


Title :   SLC5A8-Mediated Switching of STAT3 from a Pro-Oncogenic Signal into a Pro-Apoptotic Signal in Breast Cancer


Descriptive Note : Final rept. 1 Jun 2008-31 May 2011


Corporate Author : MEDICAL COLL OF GEORGIA AUGUSTA RESEARCH INST


Personal Author(s) : Thangaraju, Muthusamy


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a554208.pdf


Report Date : Jun 2011


Pagination or Media Count : 56


Abstract : Overall our findings demonstrated that the novel tumor suppressor SLC5A8 is necessary to mediate the pro-apoptotic function of STAT3 in the normal mammary epithelial cells. To support our findings, we observed that the functional inactivation of SLC5A8 is associated with mammary gland involution delay, hyperplasia, and early onset of mammary tumorigenesis as well as accelerated lung metastasis. SLC5A8 associated tumor suppression is mainly linked to its effects of transporting the physiological substrate, butyrate, in to the mammary epithelium. Interestingly, mammary gland specific Slc5a8 expression (MMTV-Slc5a8-Tg) is associated with precocious mammary gland involution and significant protection against MMTV-Neu-Tg and MMTV-HRas-Tg induced mammary tumor and its associated lung metastasis. Further, STAT3 and SLC5A8 are necessary for the milk stasis induced cellular apoptosis in mammary epithelium. Functional inactivation of either Stat3 or Slc5a8, using the Stat3 and Slc5a8 siRNAs, efficiently blocks milk stasis induced apoptosis in mammary epithelial cells. In addition, continuous release of butyrate (90 days release) provokes mammary gland involution by activating the apoptotic signaling in the mouse mammary glands. Over all our results provide in vivo evidence that functional Slc5a8 is necessary to mediate Stat3 induced apoptosis in mammary epithelium as well as to prevent the Stat3 associated mammary tumorigenesis.


Descriptors :   *MAMMARY GLANDS , *NEOPLASMS , BREAST CANCER , BUTYRATES , CELLS(BIOLOGY) , EPITHELIUM , LUNG , METASTASIS , VACCINES


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE