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Figure 8 | Molecular Cancer

Figure 8

From: MYC regulates the unfolded protein response and glucose and glutamine uptake in endocrine resistant breast cancer

Figure 8

Glutamine in glucose-deprived conditions activates the UPR. A, Cells were plated at 70% confluence. 24 hr later, media was changed to 0, 2, or 4 mM glutamine alone or in presence of 12 mM glucose. Western blot analysis showed Increased levels of GRP78, IRE1a, phospho-JNK, CHOP and decreased levels of BCL2 were present in LCC1 (right) and LCC9 (left) cells in glutamine-only conditions. MYC protein levels were highest when both glucose and glutamine are present; MYC is undetectable when these metabolites are absent in the media. MYC expression in the presence of glutamine-only, but not in presence of glucose-only, conditions correlated with increased expression of UPR proteins. B, Knockdown of MYC for 24 h was followed by media change to either glucose + glutamine, glucose-only, glutamine-only or no glucose + no glutamine conditions for another 48 h. Western blots analysis showed that a decrease in MYC protein levels correlated with an increase in the UPR proteins IRE1α and phospho-JNK(Thr183/Ty4185), and the autophagosome formation marker LC3II, and the autophagosome cargo degradation marker p62/SQSTM1. GRP78 was also increased in glucose + glutamine, glucose-only and no glucose + no glutamine conditions but robust expression of GRP78 in glutamine-only conditions was not affected by MYC siRNA. Total levels of JNK did not change.

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