Neurotensin Receptor 1 (NTSR1) Overexpression in Breast Carcinomas Is Common and Independent
of ER/PR/Her2 Expression
16
Figure 5. NTSR1 expression (% of high expression) in
breast carcinomas with regards to the histologic grade
(MBR grading system). A significant difference existed be-
tween Grade 1 and Grade 3 tumors.
lines have demonstrated the significant growth-inhibitory
effects of various means of NTSR1 blockage. Earlier
studies using SR48692, the first NTSR1 antagonist has
shown a significant reduction of cancer cell proliferation
in ex vivo cell culture or xenografted model [18,19]. In
the study of Souaze et al., small interfering RNA knock-
down of NTSR1 in xenografted MDA-MB-231 cells re-
sulted in a 70% decrease in tumor growth as compared to
wild-type cells [5]. In the study of Heakal et al, nanoli-
posomal short-chain ceramide, a chemical that can in-
hibit agonist-dependent translocation of NTSR1, was
found to significantly inhibit NTSR1-mediated MDA-
MB-231 breast cancer progression (mitogenesis, migra-
tion, and matrix metalloproteinase activity) [8]. Casti-
llo-Rodriguez et al. recently developed a neurotensin-
polyplex that transfects therapeutic genes into NTSR1-
expressing breast cancer cells (MDA-MB-231 cells) and
kills tumor cells in both in vitro and in vivo models [20].
Unfortunately, to the best knowledge of the authors, a
clinically usable NTSR1 antagonist is still not available.
The exact efficacy of the proposed anti-NTSR1 treatment
awaits validation through future study, provided a clini-
cally applicable drug becomes a reality in the near future
with the recent better understanding of the chemical
structure of NTSR1 [21].
5. Acknowledgements
This study was supported by the Calgary Laboratory
Services (CLS, RS10-534). Ms. Michelle Darago pro-
vided very helpful technical support.
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