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. 2013 Apr 15:9:80.
doi: 10.1186/1746-6148-9-80.

Activation of mammalian target of rapamycin (mTOR) in triple negative feline mammary carcinomas

Lorella Maniscalco  1 , Yolanda Millán, Selina Iussich, Mauro Denina, Raquel Sánchez-Céspedes, Francesca Gattino, Bartolomeo Biolatti, Nobuo Sasaki, Takayuki Nakagawa, Maria Flavia Di Renzo, Juana Martín de Las Mulas, Raffaella De Maria
Affiliations

Activation of mammalian target of rapamycin (mTOR) in triple negative feline mammary carcinomas

Lorella Maniscalco et al. BMC Vet Res. .

Abstract

Background: Triple negative breast cancer (TNBC) in humans is defined by the absence of oestrogen receptor (ER), progesterone receptor (PR) and HER2 overexpression. Mammalian target of rapamycin (mTOR) is overexpressed in TNBC and it represents a potential target for the treatment of this aggressive tumour. Feline mammary carcinoma (FMC) is considered to be a model for hormone-independent human breast cancer. This study investigated mTOR and p-mTOR expression in FMC in relation to triple negative (TN) phenotype.

Results: The expression of mTOR, p-mTOR, ERα, PR and HER2 was evaluated in 58 FMCs by immunohistochemistry and in six FMC cell lines by Western blot analysis. 53.5% of FMC analyzed were ER, PR, HER2 negative (TN-FMC) while 56.9% and 55.2% of cases expressed mTOR and p-mTOR respectively. In this study we found that m-TOR and p-mTOR were more frequently detected in TN-FMC and in HER2 negative samples.

Conclusions: In this study, we demonstrate that there is also a FMC subset defined as TN FMC, which is characterised by a statistically significant association with m-TOR and p-mTOR expression as demonstrated in human breast cancer.

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Figures

Figure 1
Figure 1
DFI in patients with TN and no-TN feline mammary carcinomas. Kaplan–Meier estimates for disease free interval probability in TN-FMCs (TN) and no TN_FMCs (no-TN) (P >0.05).
Figure 2
Figure 2
mTOR expression in tubulopapillary carcinoma. a. Mammary gland. I grade tubulopapillary carcinoma. Neoplastic cells are characterised by diffuse and moderate cytoplasmic immunopositivity for mTOR. Streptavidin-biotin-peroxidase method. Mayer’s haematoxylin counterstaining. Scale bar = 50 μM b. Mammary gland. III grade tubulopapillary carcinoma. Neoplastic cells are characterised by diffuse and moderate cytoplasmic immunopositivity for mTOR. Streptavidin-biotin-peroxidase method. Mayer’s haematoxylin counterstaining. Scale bar = 50 μM.
Figure 3
Figure 3
- phospho-mTOR expression in tubulopapillary carcinoma. Mammary gland. III grade tubulopapillary carcinoma. About 60% of neoplastic cells are characterised by strong nuclear immunopositivity for p-mTOR. Streptavidin-biotin-peroxidase method. Mayer’s haematoxylin counterstaining. Scale bar = 100 μM.
Figure 4
Figure 4
Western blot. a. Western blot analysis of HER2, oestrogen receptor α (ERα), progesterone receptor (PR), mTOR and p-mTOR expression in FYCp (lane 1), P248m (lane 2), FMCp (lane 3), FMCm (lane 4), FKNp (lane 5) and FNNm (lane 6) cell lines. α Tubulin expression was used as the loading control. b. Measure of band intensity normalized to α tubulin. Error bars demonstrate standard deviation.
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