Table 5.
Common biofunctions and associated differentially expressed genes between progestins without and with addition of E2. E2: estradiol; P4: progesterone; MPA: medroxyprogesterone acetate; LNG: levonorgestrel; NETA: norethindrone acetate; Vh: vehicle; DEG: differentially expressed genes.
| Common Functions between Progesterone and Testosterone Structurally Related Progestins (Predicted Activation, z-score≥2) | Common DEG Progestins Related to Progesterone (P4/MPA) | Common DEG Progestins Related to Testosterone (LNG/NETA) | |
|---|---|---|---|
| −E2 | Cell viability of tumor cell lines (Decreased) | ABCA1, AK5, APOE, CCL2, CD200, DUSP6, FKBP5, GUCY1A3, INSR, KRT19, MAPK3K4, NTF3, SMAD3, TOX, ZBTB16 | AK5, AKAP13, APOE, ASAH1, BCL6, BDNF, BEX2, CASP1, CAV1, CCL2, CCND1, CD200, CDH2, CTGF, CXCL12, DNM1, DUSP6, FGFR1, FKBP5, GDF15, GUCY1A3, HMOX1, ID4, IL6, INPP5A, INSR, IRS2, JMJD1C, KIT, KRT19, LIMK2, MAP3K4, MCOLN1, NFAT5, NR1D1, NRP1, NTF3, PGRMC1, PIK3R1, PLAU, PLK2, POLB, PTPN11, PTPRK, SMAD3, TOX, TRIB2, UGCG, VEGFA, WEE1, ZBTB16 |
| +E2 | Differentiation of fibroblasts (Decreased) | CCL2, CD44, DKK1, F2RL1, IL6, PDE5A | CCL2, DKK1, F2RL1, IL6, PDE5A |
| Growth of connective tissue (Decreased) | CCL2, CCND1, CD44, CDH13, CTGF, CXCL12, FGF1, FGF7,, FGF9, FOXO1, GREM1, IGFBP4, IL6, PDE5A, PDGFD, PLAU, PTPRK, RUNX1T1, SFRP1, SMAD3, SPRY2, THRB, TMPO, WNT2 | CCL2, CCND1, CD83, CDH13, CTGF, CXCL12, FGF1, FGF7, FGF9, FGFR1, FOXO1, GREM1, IGFBP4, IL6, PDE5A, PDGFC, PLAU, PRDX4, PTPRK, RUNX1T1, SFRP1, SMAD3, SPRY2, THRB, TMPO, WNT2 | |
| Invasion of cells (Decreased) | ABLIM1, BDKRB1, BDNF, CAV1, CCL2, CCND1, CD44, CDH13, CDH2, CFH, CNR1, CTGF, TSB, CTSH, CTSL, CXCL12, DKK1, DOCK4, DRAM1, DUSP6, EFNB3, ELMO1, ETV1, ETV4, ETV5, FHL2, FUT8, GDF15, HMOX1, HTRA1, IL6, IRS2, JUNB, JUP, KIT, KRT19, LCP1, LIMA1, LIMK2, LPAR1, MGAT5, MMP16, MMP3, MSI2, NFAT5, NRP1, NRP2, PDLIM1, PIK3R1, PLAU, PTPRK, RECK, RGS4, SATB1, SEMA5A, SERPINE1, SFRP1, SMAD3, SPARCL1, SPRY2, SPSB1, TCF4, TFAP2C | ACSL4, BDKRB1, BDNF, CAV1, CCL2, CCND1, CDH13, CDH2, CFH, CNR1, CTGF, CTSB, CTSH, CTSL, CXCL12, DIAPH2, DKK1, DOCK4, DPYSL3, DRAM1, DUSP6, EFNB3, ELMO1, ESR1, ETV1, ETV4, ETV5, FGFR1, FHL2, FUT8, GDF15, HMOX1, HTRA1, ID4, IL6, IRS2, JUNB, JUP, KIT, KRT19, LCP1, LIMA1, LIMK2, LOXL2, LPAR1, MGAT5, MMP3, MSI2, NFAT5, NRP1, NRP2, PDLIM1, PGR, PIK3R1, PLAU, PTPRK, RECK, RGS4, SATB1, SEMA5A, SERPINE1, SFRP1, SMAD3, SPARCL1, SPRY2, SPSB1, TCF4, TFAP2C, TGFB3, TGFBI, TMPO, VEGFA, ZBTB16 | |
| Invasion of tumor cell lines (Decreased) | ABLIM1, BDKRB1, BDNF, CAV1, CCL2, CCND1, CD44, CDH13, CDH2, CFH, CNR1, CTGF, CTSB, CTSH, CXCL12, DKK1, DOCK4, DRAM1, DUSP6, EFNB3, ELMO1, ETV1, ETV4, ETV5, FHL2, FUT8, GDF15, HMOX1, HTRA1, IL6, IRS2, JUNB, KIT, KRT19, LCP1, LIMA1, LIMK2, LPAR1, MGAT5, MMP16, MMP3, MSI2, NFAT5, NRP1, NRP2, PDLIM1, PIK3R1, PLAU, PTPRK, RECK, SATB1, SEMA5A, SFRP1, SMAD3, SPARCL1, SPRY2, SPSB1, TCF4 | ACSL4, BDKRB1, BDNF, CAV1, CCL2, CCND1, CDH13, CDH2, CFH, CNR1, CTGF, CTSB, CTSH, CXCL12, DIAPH2, DKK1, DOCK4, DPYSL3, DRAM1, DUSP6, EFNB3, ELMO1, ESR1, ETV1, ETV4, ETV5, FGFR1, FHL2, FUT8, GDF15, HMOX1, HTRA1, ID4, IL6, IRS2, JUNB, KIT, KRT19, LCP1, LIMA1, LOXL2, LPAR1, MGAT5, MMP3, MSI2, NFAT5, NRP1, NRP2, PDLIM1, PGR, PIK3R1, PLAU, PTPRK, RECK, SATB1, SEMA5A, SFRP1, SMAD3, SPARCL1, SPRY2, SPSB1, TCF4, TFAP2C, TGFB3, TGFBI, TMPO, VEGFA | |
| Migration of breast cancer cell lines (Decreased) | CCL2, CCND1, CD44, CDH2, CTGF, CTSL, CXCL12, DUSP6, FGF1, FGF7, GAB1, IL6, ITGA6, KRT19, NRP1, PIK3R1, PLAU, SEMA3C, SERPINE1, SMAD3, TFAP2C, TGFB3, THRB, TNFRSF21 | ACSL4, CCL2, CCND1, CDH2, CTGF, CTSL, CXCL12, DUSP6, ESR1, FGF1, FGF7, GAB1, IL6, KRT19, NRP1, PGR, PIK3R1, PLAU, SEMA3C, SERPINE1, SLC16A4, SMAD3, TFAP2C, TGFB3, THRB, TNFRSF21, VEGFA | |
| Migration of tumor cell lines (Decreased) | BDKRB1, BDNF, CAV1, CCL2, CCND1, CD44, CDH13, CDH2, CTGF, CTSB, CTSH, CTSL, CXCL12, DUSP6, EFNB3, ELMO1, ETV4, ETV5, F2RL1, F3, FGF1, FGF7, FHL2, GAB1, GDF15, HMOX1, HTRA1, GFBP4, IL6, ITGA6, ITPR1, JUP, KDR, KIT, KRT19, LIMK2, LPAR1, LTBP2, MGAT5, MME, MMP19, MMP3, MYO10, NRP1, NRP2, NTF3, PDLIM1, PEAK1, PIK3R1, PLAU, PLCL1, PTGER4, PTPN11, PTPRK, RAP2A, RHOU, SEMA3C, SEMA5A, SERPINE1, SMAD3, SPARCL1, SPRY2, SPSB1, TCF4, TFAP2C, TGFB3, TGFBI, THRB, TMPO, TNFRSF21 | ACSL4, BDKRB1, BDNF, CAV1, CCL2, CCND1, CDH13, CDH2, CTGF, CTSB, CTSH, CTSL, CXCL12, DUSP6, EFNB3, ELMO1, ESR1, ETV4, ETV5, F2RL1, F3, FGF1, FGF7, FGFR1, FHL2, GAB1, GDF15, HMOX1, HTRA1, IGFBP4, IL6, ITPR1, JUP, KIT, KRT19, LPAR1, LTBP2, MGAT5, MME, MMP19, MMP3, MYO10, NRP1, NRP2, NTF3, PDLIM1, PEAK1, PGR, PIK3R1, PLAU, PLCL1, PTGER4, PTPN11, PTPRK, RAP2A, RHOU, SEMA3C, SEMA5A, SERPINE1, SH3PXD2B, SLC16A4, SMAD3, SPARCL1, SPRY2, SPSB1, TBX3, TCF4, TFAP2C, TGFB3, TGFBI, THRB, TMPO, TNFRSF21, VEGFA |