title: Rapamycin induces apoptosis when autophagy is inhibited in T-47D mammary cells and both processes are regulated by Phlda1.
abstract: Autophagy is an evolutionarily conserved lysosomal degradation pathway and plays a critical role in the homeostatic process of recycling proteins and organelles. Functional relationships have been described between apoptosis and autophagy. Perturbations in the apoptotic machinery have been reported to induce autophagic cell deaths. Inhibition of autophagy in cancer cells has resulted in cell deaths that manifested hallmarks of apoptosis. However, the molecular relationships and the circumstances of which molecular pathways dictate the choice between apoptosis and autophagy are currently unknown. This study aims to identify specific gene expression of rapamycin-induced autophagy and the effects of rapamycin when the autophagy process is inhibited. In this study, we have demonstrated that rapamycin is capable of inducing autophagy in T-47D breast carcinoma cells. However, when the autophagy process was inhibited by 3-MA, the effects of rapamycin became apoptotic. The Phlda1 gene was found to be up-regulated in both autophagy and apoptosis and silencing this gene was found to reduce both activities, strongly suggests that Phlda1 mediates and positively regulates both autophagy and apoptosis pathways.
authors.affiliation: Advanced Medical and Dental Institute, Universiti Sains Malaysia, Pulau Pinang, Malaysia.
authors.forename: Ahmed Ismail Hassan
authors.initials: AI
authors.lastname: Moad
authors.forename: Tengku Sifzizul Tengku
authors.initials: TS
authors.lastname: Muhammad
authors.forename: Chern Ein
authors.initials: CE
authors.lastname: Oon
authors.forename: Mei Lan
authors.initials: ML
authors.lastname: Tan
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D020123:Sirolimus / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C491923:PHLDA1 protein, human; D014157:Transcription Factors; C025946:3-methyladenine; D000225:Adenine; D020123:Sirolimus