Investigation of HTR1B and TPH1 gene in colon cancer cell lines and their orthologuses in hypoxia in C. elegans

Serotonin (5-Hydroxytryptamine, 5-HT) is an amine with important functions. This amine is synthesized from L-tryptophan by tryptophan hydroxylase (TPH). Serotonin shows its effects through serotonin receptors located in the membrane. Serotonin has been shown to have a potential effect on proliferation, invasion, spread in cancer cells and angiogenesis in tumors. Especially 5-HT 1A, 5-HT 1B, 5-HT 1D and 5-HT 2A receptors have been studied in various cancers, but their effects in colon cancer are not fully understood due to their complexity. Since tumor cells divide uncontrollably, they consume a lot of energy and their microenvironment is in a hypoxic condition. This microenvironment may cause changes in the regulation of genes. In this thesis study, the changes in HTR1B and TPH1 genes with hypoxia in colon cancer cell models were examined at the mRNA and protein levels. In addition, the expressions of the ser-4 and cTPH genes, which are orthologs of these genes, were examined in hypoxic conditions in the model organism C.elegans. In the bioinformatic analyses, it was seen that these two genes were 87% similar and affected similar cellular signaling pathways. It was determined that the expression of HTR1B and TPH1 increased at the mRNA level in the HT-29 colon cancer cell model, that HTR1B increased and TPH1 decreased in the SW480 colon cancer cell model, and that HTR1B increased and TPH1 decreased in the HUVEC healthy human endothelial cell model. In C.elegans, it was determined that the mRNA levels of the ser-4 and cTPH genes increased. The effects of the HTR1B gene on various cell lines play a critical role in understanding the complex dynamics of the serotoninergic system. As a result, the effects of the HTR1B and TPH genes on various cell lines constitute an important step in understanding the functionality of this gene in cancer and its potential therapeutic uses.