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Figure 3 | Cancer Cell International

Figure 3

From: Upstream molecular signaling pathways of p27 (Kip1) expression in human breast cancer cells in vitro: differential effects of 4-hydroxytamoxifen and deficiency of either D-(+)-glucose or L-leucine

Figure 3

Schematic diagram of the four different upstream molecular signaling pathways of p27 expression that could lead to either increased or decreased expression of p27 in human breast cancer cells in vitro. (a) Previously, we identified and reported four different upstream molecular signaling pathways of the expression of p27 [1, 2]. We also reported previously that 4-hydroxytamoxifen - but not tamoxifen - up-regulated the expression of p27 by using pathway #1 which consists mainly of receptor tyrosine kinases (RTKs) and mTORC1 [2]. Now, we hypothesize that (i) moderate increase in the concentration of D-(+)-glucose down-regulates and (ii) deficiency of D-(+)-glucose or certain L-amino acids up-regulates the expression of p27 using pathway #2 which consists mainly of AMPK and mTORC1. (b) We also identified and reported previously two additional upstream molecular signaling pathways - namely #3 and #4 - of the expression of p27 [1, 2]. (c and e) Western immunoblot analysis of the effects of D-(+)-glucose deficiency, DMSO, tamoxifen and 4-hydroxytamoxifen on the expression of p27 protein in MDA-MB-231 cells. (d and e) Western immunoblot analysis of the effects of the deficiency of L-leucine, L-methionine or L-cysteine on the expression of p27 protein in these cells. All assays were performed in triplicates and repeated three times.

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