Maria Elena Sales
UBA, Argentina
Title: Muscarinic acetylcholine receptors can act as a two sided coin by acting as tumor promoters or as therapeutic targets in breast cancer
Biography
Biography: Maria Elena Sales
Abstract
We have demonstrated that muscarinic acetylcholine receptors (mAChR) are involved in breast cancer progression in different experimental models. In mice, we demonstrated that mAChR are expressed in three distinct spontaneous mammary adenocarcinomas, while they were absent in normal epithelial mammary cells. In humans, we detected the expression of mAChR in breast tumor homogenates as well as, in two different tumor cell lines MDA-MB-231 and in MCF-7. The latter exhibits a marked expression of 3 and 4 subtypes. To analyze the role of mAChR in human breast oncogenesis, we transfected the non tumorigenic mammary cell line, MCF-10A, which does not express mAChR with these receptors, and obtained three stable clones: MCF-10A-mAChR3, MCF-10A-mAChR4 and MCF-10A-mAChR3 & 4, the latter one resembled to MCF-7 cell line. These clones formed spheroid structures in vitro, and responded to the stimulation with carbachol. Clones grew to form tumors in NUDE mice, while MCF-10A cells were unable to form spheroids in culture or to grow in vivo. Taking into account these previous results, as well as the fact that the addition of a combination of paclitaxel plus carbachol at low concentrations to murine breast cancer cells promotes tumor cell lysis, mainly via apoptosis, we analyzed the role of mAChR as therapeutic targets in human breast cancer. We confirmed that this combination was equally useful to trigger cell death in MCF-7 and MDA-MB-231 human adenocarcinomas, while it was innocuous in MCF-10A cells. These results let us speculate, about the possibility of using of this type of therapy in breast cancer.