05-14-5 pm
也就是說
GR+DEX 本可活化一些和invasion/migration相關的 genes (in 231), 而有ER的細胞如MCF7則抑制了這些功能。
Therefore, next time you should look for
a. DEX and metastasis
b. ER-mediated repression of metastasis
c. combine both a and b.
I compiled all the YSL-related NSC grants in “大家的國科會”
I compiled steroid, glucocorticoid, dexamethasone, 鄭醫師國科會in “GR and ER”.
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05-14-3pm
1. steroid biosynthesis vs. steroid hormone (progesterone, androgen, estrogen and cortisone)
2. Dexamethasone (Dex) is a glucocorticoid, it is supposed to be long-live and binds to GR receptor.
3. YSL and his colleagues found that adding Dex to three TNBC cells (MB231, BT549 and HCC1954(?)) increased their tumorigenicity; while adding Dex to luminal type BrCA cells (T47D and MCF7) has not effect. Of note, tumorigenicity was determined by (1) formation of colonies on soft agar (2) clongenicity on plates (3) mouse model (here YSL also observed self-seeding phenomenon)
4. Other observations with TNBC+Dex include (1) no change in cell proliferation (2) increase in wound healing (3) invasive migration (specifically, MDA-MB231, but not MCF7, migrates toward Dex-treated HMEC or MCF10A on the bottom of a transwell)
5. Expression array was conducted on Dex-treated 231 cells to look for Oncogenes of TS genes. By far, CD44, ESA, PROCR are three markers for “stem-cell” present in Dex-treated MB231 cells.
6. From wiki, activated GR is known to
- trans-activates anti-inflammatory genes (involves GRE, e.g. lipocortin 1, SLP1) and increases gluconeogenesis (G-6-P and tyrosine aminotransferase)
- trans-represses pro-inflammatory genes via interacting with AP-1 and NF-KB functions (e.g. ↓ IL1B, IL4, IL5, IL8 etc).
- Disassociation: transgenic mice with GR defective in DNA binding reveled no affects on immune response but the gluconeogenesis was blocked. These model suggested that the desired anti-inflammatory function of GR is primarily through “trans-repression”, while the unwanted metabolic effect was via “trans-activation. This hypothesis pave the way for development of selective GR agnoists.
7. Kieth BD (2008) suggested that glucocorticoid may be detrimental for treating lung cancer. And YSL also found that GR may decrease the chemosensivity in CL1-0 and CL1-5.
8. In S. Conzenas mini review: GR was found to decrease breast cancer cell apoptosis.
9. Must read Vaidya’s “role of GR in breast cancer” (pdf yes)
10. Must read ERa-regulated genes in MCF7 and ZR75-1 (Here) (pdf yes)
11. GR signaling in BrCA. (Review paper, but not accessible)