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TAAR1 levels and sub-cellular distribution are cell line but not breast cancer subtype specific.

Authors
  • Pitts, Mallory S1
  • McShane, Josh N1
  • Hoener, Marius C2
  • Christian, Sherri L3
  • Berry, Mark D4
  • 1 Department of Biochemistry, Memorial University of Newfoundland, 232 Elizabeth Ave, St. John's, NL, A1B 3X9, Canada. , (Canada)
  • 2 Neuroscience, Opthalmology and Rare Diseases DTA, pRED, Roche Innovation Center Basel, F. Hoffman-La Roche, Basel, Switzerland. , (Switzerland)
  • 3 Department of Biochemistry, Memorial University of Newfoundland, 232 Elizabeth Ave, St. John's, NL, A1B 3X9, Canada. [email protected] , (Canada)
  • 4 Department of Biochemistry, Memorial University of Newfoundland, 232 Elizabeth Ave, St. John's, NL, A1B 3X9, Canada. [email protected] , (Canada)
Type
Published Article
Journal
Histochemistry and cell biology
Publication Date
Aug 01, 2019
Volume
152
Issue
2
Pages
155–166
Identifiers
DOI: 10.1007/s00418-019-01791-7
PMID: 31111198
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Trace amine-associated receptors are G protein-coupled receptors of which TAAR1 is the most well-studied. Recently, Vattai et al. (J Cancer Res Clin Oncol 143:1637-1647 https://doi.org/10.1007/s00432-017-2420-8 , 2017) reported that expression of TAAR1 may be a marker of breast cancer (BC) survival, with a positive correlation also suggested between TAAR1 expression and HER2 positivity. Neither a role for TAAR1 in breast tissue, nor in cancer, had previously been suspected. We, therefore, sought to provide independent validation and to further examine these putative relationships. First, a bioinformatic analysis on 58 total samples including normal breast tissue, BC-related cell lines, and tumour samples representing different BC sub-types found no clear correlation between TAAR1 mRNA levels and any BC subtype, including HER2 + . We next confirmed the bioinformatics data correlated to protein expression using a well validated anti-human TAAR1 antibody. TAAR1 mRNA levels correlated with the relative intensity of immunofluorescence staining in six BC cell lines (MCF-7, T47D, MDA-MB-231, SKBR3, MDA-MB-468, BT-474), but not in the MCF-10A immortalized mammary gland line, which had high mRNA but low protein levels. As expected, TAAR1 protein was intracellular in all cell lines. Surprisingly MCF-7, SKBR3, and MDA-MB-468 showed pronounced nuclear localization. The relative protein expression in MCF-7, MDA-MB-231, and MCF-10A lines was further confirmed by semi-quantitative flow cytometry. Finally, we demonstrate that the commercially available anti-TAAR1 antibody has poor selectivity, which likely explains the lack of correlation with the previous study. Therefore, while we clearly demonstrate variable expression and sub-cellular localization of TAAR1 across BC cell lines, we find no evidence for association with BC subtype.

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