Unknown,Transcriptomics,Genomics,Proteomics

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Genetic deletion or pharmacologic blockade of the amino acid transporter Slc6a14 in mice suppresses breast cancer induced by Polyoma middle T oncogene


ABSTRACT: Tumor cells have an increased need for amino acids. Mammalian cells cannot synthesize essential amino acids; they must obtain these amino acids via specific transporters. Glutamine, though a non-essential amino acid, is critical for tumor cells (glutamine addiction). Entry of amino acids into tumor cells is enhanced by upregulation of specific transporters. If the transporters that are specifically induced in tumor cells are identified, blockade of the induced transporters would constitute a logical strategy for cancer treatment. The transporter SLC6A14 is unique and transports all essential amino acids as well as glutamine and is expressed only at low levels in normal tissues, but induced in colon cancer and in ER+ breast cancer. We have now established the potential of this transporter as a drug target for breast cancer treatment using genetic and pharmacologic approaches. We then examined the progression of breast cancer in Polyoma middle T antigen (Py-MT) Tg mouse on Slc6a14+/+ and Slc6a14-/- background using microarray analysis. We have used three Affy-chips for each tumor sample (Group 1: WT/PyMT; Group 2: Slc6a14-KO/PyMT). Three biological replicates were used for each group.

ORGANISM(S): Mus musculus

SUBMITTER: Pachiappan Arjunan 

PROVIDER: E-GEOD-56612 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Deletion of the amino acid transporter Slc6a14 suppresses tumour growth in spontaneous mouse models of breast cancer.

Babu Ellappan E   Bhutia Yangzom D YD   Ramachandran Sabarish S   Gnanaprakasam Jaya P JP   Prasad Puttur D PD   Thangaraju Muthusamy M   Ganapathy Vadivel V  

The Biochemical journal 20150513 1


SLC6A14 mediates Na(+)/Cl(-)-coupled concentrative uptake of a broad-spectrum of amino acids. It is expressed at low levels in many tissues but up-regulated in certain cancers. Pharmacological blockade of SLC6A14 causes amino acid starvation in estrogen receptor positive (ER+) breast cancer cells and suppresses their proliferation in vitro and in vivo. In the present study, we interrogated the role of this transporter in breast cancer by deleting Slc6a14 in mice and monitoring the consequences o  ...[more]

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