Abstract 3787: Serotonin signaling plays a role in regulation of autophagy in breast cancer cells
Authors: Alpay Neslihan , Tekedereli Ibrahim , Lopez-Berestein Gabriel , Dalby Kevin , Ozpolat Bulent 
Published: June 2012

Breast cancer is the second most common cause of cancer death in women in the United States, 40,000 dying of this disease each year. One out of eight women will be diagnosed with breast cancer in their lifetime. There are several treatments for breast cancer, such as surgery, radiation therapy, chemotherapy, and hormone therapy, but still 5 year survival is less than 40% in advance cases. Due to the high incidence and mortality associated with this cancer better understanding of the biology of the disease and development of new treatments are urgently needed. The actions of local physiological mediators in the context of breast cancer are poorly understood. Serotonin (5HT, 5-hydroxytryptamine) is a critical local regulator of epithelial homeostasis in the breast and other organs. Serotonin is more commonly known as a monoamine neurotransmitter and a mediator of depression if the levels drop in the brain. Serotonin has been implicated in epithelial homeostasis of the breast, lung, pancreas, liver, and prostate. Deregulation of serotonin signaling in these epithelia may be associated with various pathologies, including cancer. Previous and our studies suggested serotonin can induce proliferation of some cancer cell lines. On the other hand serotonin can induce apoptosis or induce cell proliferation depending on the cancer type. Serotonin is believed to function as a growth factor working as an autocrin manner. Also tryptophan hydroxylase 1 (TPH1), rate-limiting step in 5-HT synthesis, has been shown to be overexpressed in breast cancer cell lines and biopsy samples from patients. The effect of serotonin signaling and its role in survival of breast cancer cells has not been well understood. We tried to address the questions that what is the role of serotonin signaling in breast cancer survival and if serotonin inhibits apoptosis or autophagy? We found that serotonin slightly induced cell proliferation in estrogen receptor positive MCF-7 breast cancer cells. Because autophagy is implicated as a survival pathway in some cancers we also examined if serotonin induces autophagy in MCF7 ER+ breast cancer cells. We found that serotonin induces autophagy that is detected Acridine orange staining and FACS analysis and LC-3 II induction, a hallmark of autophagy, by western blot analysis in MCF7 cells after serotonin treatment for 4 hours. We found that serotonin (10 uM) induces expression of cyclinD1, NF-kB and mTOR and leads induction of ERK and AMPK pathway as indicated by increased phosphorylation of ERK1/2 and AMPK (Thr 172), both of which are known to mediate autophagy. We are currently testing if induction ERK and AMPk signaling is involved in induction autophagy in these cells using specific inhibitors of MEK. In conclusion our studies showed for the first that induction of serotonin signaling induces autophagy in ER+ breast cancer cells.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3787. doi:10.1158/1538-7445.AM2011-3787