Implications of TGF-β in the early progression of breast cancer

Marianela Sciacca¹, Macarena Zambrano¹, Lina Marino², Ana Maria Eiján¹, Catalina Lodillinsky¹

The TGF-β pathway activates the EMT process and enhances the stemness of normal and cancerous breast cells. This suggests that TGF-β is implicated in the early stages of breast cancer progression. On this basis, we propose to understand the implication of TGF-β in the dialogue between the two populations that conform the mammary duct: luminal cells (LEP) and myoepithelial cells (MEP). The cellular mouse model LM38 is composed of LM38-LP (MEP and LEP), LM38-HP (LEP) and LM38-D2 (MEP). Previously, we showed that only LM38-LP was able to develop DCIS tumors after intraductal injections, suggesting that bi-cellular interaction could confer an advantage for tumor formation and progression. Moreover, treatment with conditioned medium of MEP induced viability on LM38-LP. LM38-D2 showed higher levels of TGF-β1 mRNA than LM38-LP (qPCR, p<0.05). LM38 cells were treated with a recombinant TGF-β1 (1ng/µl) and an inhibitor of its receptor SB431542 (10 and 20µM). We could observe that TGF-β1 treatment increased 40 percent the viability of LM38-LP compared to the control, which is reduced in the presence of SB431542 (CV, p<0.05, p<0.001). LM38-D2 tumors showed higher expression levels on TGF-β1 than LM38-LP (IHQ, p=0.03). Expression of TGF-β1 presented a heterogeneous pattern in LM38-LP tumors which requires further characterization. These results suggest that TGF-β1 is one of the contributing factors in the LEP-MEP dialogue and could be involved in the DCIS-IDC transition.