Moad, Ahmed Ismail Hassan
(2013)
The Molecular Mechanisms Of Rapamycininduced
Autophagy And Apoptosis In T-47d Breast
Carcinoma Cells.
PhD thesis, Universiti Sains Malaysia.
Abstract
Autophagy is an evolutionarily conserved lysosomal degradation pathway
that leads to degradation of proteins and entire organelles and subsequently plays a
crucial role in the homeostatic process of recycling proteins and organelles.
Autophagy is an important biological mechanism that enables cell survival and to
induce death of damage cells. There is increasing evidence that autophagy progresses
to autophagic cell death when the process is over-stimulated. Functional relationships
have been described between apoptosis (Type I cell death) and autophagic cell death
(Type II cell death). However, the molecular relationships and the circumstances of
which molecular pathways dictate the choice between autophagy and apoptosis are
currently unknown. Autophagy is regulated by the mammalian target of rapamycin
(mTOR) kinase pathway. The mTOR are known to inhibit the autophagy process and
subsequently lead to tumor development. As a strategy, rapamycin, a known
inhibitor of mTOR, was used as an autophagy inducer and 3-methyladenine (3MA)
as a classical inhibitor of autophagy. In the present study, a systematic global gene
expression was investigated in rapamycin-induced autophagy and the effects of
rapamycin when autophagy process is inhibited. The findings have demonstrated that
rapamycin was capable of inducing autophagy in T-47D breast carcinoma cells.
However, when autophagy was inhibited by 3MA, rapamycin appeared to induce
apoptosis in these breast cells.
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