| Material . | Method . | Study summary . | Reference . |
|---|---|---|---|
| normal mammary epithelial cell | autocrine GH | oncogenic transformation and in vivo tumor growth | (32, 154, 155) |
| BC cell lines, patient samples | RNA and protein | GH and GHR expression | (21, 35, 56, 143-146, 150-153) |
| patient samples | IHC for GHR | enriched in ER− BC samples | (145) |
| patient samples | IHC for GH, clinical correlation | GH overexpression in cancer tissue, correlates with poorer survival | (183) |
| patient sample | protein expression | tumor GHR expression correlates with aggressive metastasis | (144) |
| patient sample—IHC | correlation with tumor GH expression | tumor GH expression correlates with lymph node metastasis, tumor grade | (183) |
| autocrine GH in cell line, patient sample-RNA | RNA expression | autocrine GH expression intact in metastatic tumors | (35, 36) |
| patient data | GWAS data analyses | GH signaling pathway—one of top 3 pathways associated with BC | (133) |
| human patients | hypophysectomy | high rate of remission | (134, 141, 142) |
| BC cell lines | autocrine GH | increases proliferation | (146, 156, 158) |
| MCF7 cell line | autocrine GH | inhibits growth suppressors | (184) |
| MCF7 cell line | autocrine GH | resistance to chemotherapy (doxorubicin) induced apoptosis | (185) |
| MCF7 cell line | autocrine GH | increases DDR and resistance to starvation induced apoptosis | (156, 157, 186) |
| MCF7-hGH cells | GHRA (B2036) treatment | increases starvation induced apoptosis | (157) |
| BC cells | autocrine GH | resistance to starvation induced apoptosis | (187) |
| BC cells | autocrine GH | resistance to radiotherapy induced apoptosis | (188) |
| BC cells | autocrine GH | resistance to chemotherapy (MMC, doxorubicin, cisplatin) induced apoptosis | (162, 189) |
| BC cells | autocrine GH | resistance to oxidative stress induced apoptosis | (190) |
| ER+ and TNBC cells | autocrine GH | resistance to chemotherapy (MMC) induced apoptosis | (162) |
| ER+ and TNBC cells | autocrine GH + GHRA (B2036) treatment | sensitized to radiotherapy induced apoptosis | (188) |
| ER+ and TNBC cells | exogenous GH + GHRA (pegvisomant) treatment | sensitized to chemotherapy (doxorubicin) induced apoptosis | (160, 163) |
| patient-derived primary cells | anti-GHR shRNA | decreases cell viability, drug efflux, sensitized to chemotherapy (docetaxel) induced apoptosis | (145) |
| multiple BC cell types | autocrine GH | induces EMT, promotes migration-invasion | (36, 159, 161, 168) |
| BC cell line | autocrine GH | promotes DNA methylation, EMT induction | (191) |
| multiple BC cell types | orthotopic xenograft—nude mice | EMT induction, metastasis, ECM remodeling, stromal fibrosis | (36, 159, 161) |
| ER− BC cell xenograft in nude mice | autocrine GH | higher rate of invasion and metastases | (162, 188) |
| nude mouse xenograft | GHRA (B2036) treatment | sensitized to MMC induced apoptosis | (162) |
| T47D xenografts—nude mice | treated with GH | tumor proliferation, potentiation of estrogen effect | (192, 193) |
| TNBC cell lines | autocrine GH | resistance to tamoxifen, curcumin induced apoptosis | (164, 165) |
| estradiol-treated parous rats + MNU | increased serum GH | increased rate of tumorigenesis | (180) |
| control vs SDR | DMBA or MNU treatment | lower tumor incidence and size in SDR | (194) |
| SDR + GH | DMBA treatment | increased tumor incidence | (195, 196) |
| tumor bearing SDR + GH | GH withdrawal | tumor regression | (197) |
| SDR + GH + doxorubicin | GH withdrawal | sensitized to doxorubicin induced apoptosis | (198) |
| hGH/bGH transgenic mice | changes in mammary tissue | neoplasia (only for hGH transgenic, not oGH or bGH) | (155) |
| C3(1)/Tag mice | crossed with GHRKO mice | GHRKO-Tag mice—suppressed tumor incidence and tumor size | (199) |
| C3(1)/Tag mice | crossed with inducible-GHRKO mice | ind-GHRKO-Tag mice—tumor growth regression | (200) |
| DMBA treatment | GHA vs control mice | lower tumor incidence, size, and burden | (201) |
| DMBA treatment | AOiGHD vs control mice | lower tumor incidence, size, and burden | (202) |
| MCF7 xenograft in nude mice | GHRA (pegvisomant) treatment | reduced proliferation, increased apoptosis, reduced tumor growth | (162, 163, 203) |
| ER− primary cell xenograft in nude mice | GHR knockdown cells | reduced tumor growth, sensitized to docetaxel induced apoptosis | (145) |
| Material . | Method . | Study summary . | Reference . |
|---|---|---|---|
| normal mammary epithelial cell | autocrine GH | oncogenic transformation and in vivo tumor growth | (32, 154, 155) |
| BC cell lines, patient samples | RNA and protein | GH and GHR expression | (21, 35, 56, 143-146, 150-153) |
| patient samples | IHC for GHR | enriched in ER− BC samples | (145) |
| patient samples | IHC for GH, clinical correlation | GH overexpression in cancer tissue, correlates with poorer survival | (183) |
| patient sample | protein expression | tumor GHR expression correlates with aggressive metastasis | (144) |
| patient sample—IHC | correlation with tumor GH expression | tumor GH expression correlates with lymph node metastasis, tumor grade | (183) |
| autocrine GH in cell line, patient sample-RNA | RNA expression | autocrine GH expression intact in metastatic tumors | (35, 36) |
| patient data | GWAS data analyses | GH signaling pathway—one of top 3 pathways associated with BC | (133) |
| human patients | hypophysectomy | high rate of remission | (134, 141, 142) |
| BC cell lines | autocrine GH | increases proliferation | (146, 156, 158) |
| MCF7 cell line | autocrine GH | inhibits growth suppressors | (184) |
| MCF7 cell line | autocrine GH | resistance to chemotherapy (doxorubicin) induced apoptosis | (185) |
| MCF7 cell line | autocrine GH | increases DDR and resistance to starvation induced apoptosis | (156, 157, 186) |
| MCF7-hGH cells | GHRA (B2036) treatment | increases starvation induced apoptosis | (157) |
| BC cells | autocrine GH | resistance to starvation induced apoptosis | (187) |
| BC cells | autocrine GH | resistance to radiotherapy induced apoptosis | (188) |
| BC cells | autocrine GH | resistance to chemotherapy (MMC, doxorubicin, cisplatin) induced apoptosis | (162, 189) |
| BC cells | autocrine GH | resistance to oxidative stress induced apoptosis | (190) |
| ER+ and TNBC cells | autocrine GH | resistance to chemotherapy (MMC) induced apoptosis | (162) |
| ER+ and TNBC cells | autocrine GH + GHRA (B2036) treatment | sensitized to radiotherapy induced apoptosis | (188) |
| ER+ and TNBC cells | exogenous GH + GHRA (pegvisomant) treatment | sensitized to chemotherapy (doxorubicin) induced apoptosis | (160, 163) |
| patient-derived primary cells | anti-GHR shRNA | decreases cell viability, drug efflux, sensitized to chemotherapy (docetaxel) induced apoptosis | (145) |
| multiple BC cell types | autocrine GH | induces EMT, promotes migration-invasion | (36, 159, 161, 168) |
| BC cell line | autocrine GH | promotes DNA methylation, EMT induction | (191) |
| multiple BC cell types | orthotopic xenograft—nude mice | EMT induction, metastasis, ECM remodeling, stromal fibrosis | (36, 159, 161) |
| ER− BC cell xenograft in nude mice | autocrine GH | higher rate of invasion and metastases | (162, 188) |
| nude mouse xenograft | GHRA (B2036) treatment | sensitized to MMC induced apoptosis | (162) |
| T47D xenografts—nude mice | treated with GH | tumor proliferation, potentiation of estrogen effect | (192, 193) |
| TNBC cell lines | autocrine GH | resistance to tamoxifen, curcumin induced apoptosis | (164, 165) |
| estradiol-treated parous rats + MNU | increased serum GH | increased rate of tumorigenesis | (180) |
| control vs SDR | DMBA or MNU treatment | lower tumor incidence and size in SDR | (194) |
| SDR + GH | DMBA treatment | increased tumor incidence | (195, 196) |
| tumor bearing SDR + GH | GH withdrawal | tumor regression | (197) |
| SDR + GH + doxorubicin | GH withdrawal | sensitized to doxorubicin induced apoptosis | (198) |
| hGH/bGH transgenic mice | changes in mammary tissue | neoplasia (only for hGH transgenic, not oGH or bGH) | (155) |
| C3(1)/Tag mice | crossed with GHRKO mice | GHRKO-Tag mice—suppressed tumor incidence and tumor size | (199) |
| C3(1)/Tag mice | crossed with inducible-GHRKO mice | ind-GHRKO-Tag mice—tumor growth regression | (200) |
| DMBA treatment | GHA vs control mice | lower tumor incidence, size, and burden | (201) |
| DMBA treatment | AOiGHD vs control mice | lower tumor incidence, size, and burden | (202) |
| MCF7 xenograft in nude mice | GHRA (pegvisomant) treatment | reduced proliferation, increased apoptosis, reduced tumor growth | (162, 163, 203) |
| ER− primary cell xenograft in nude mice | GHR knockdown cells | reduced tumor growth, sensitized to docetaxel induced apoptosis | (145) |
Abbreviations: AOiGHD, adult-onset isolated growth hormone deficiency; BC, breast cancer; DDR, DNA damage repair; DMBA, dimethylbenzanthracene; ECM, extracellular matrix; EMT, epithelial-to-mesenchymal transition; ER, estrogen receptor; GH, growth hormone; GHA mice, mice transgenic for growth hormone receptor antagonist; GHR, growth hormone receptor; GHRA, growth hormone receptor antagonist; GWAS, genome-wide association study; IHC, immunohistochemistry; MMC, mitomycin C; MNU, N-methyl-N-nitrosourea; SDR, Sprague Dawley rats; TNBC, triple-negative breast cancer.
| Material . | Method . | Study summary . | Reference . |
|---|---|---|---|
| normal mammary epithelial cell | autocrine GH | oncogenic transformation and in vivo tumor growth | (32, 154, 155) |
| BC cell lines, patient samples | RNA and protein | GH and GHR expression | (21, 35, 56, 143-146, 150-153) |
| patient samples | IHC for GHR | enriched in ER− BC samples | (145) |
| patient samples | IHC for GH, clinical correlation | GH overexpression in cancer tissue, correlates with poorer survival | (183) |
| patient sample | protein expression | tumor GHR expression correlates with aggressive metastasis | (144) |
| patient sample—IHC | correlation with tumor GH expression | tumor GH expression correlates with lymph node metastasis, tumor grade | (183) |
| autocrine GH in cell line, patient sample-RNA | RNA expression | autocrine GH expression intact in metastatic tumors | (35, 36) |
| patient data | GWAS data analyses | GH signaling pathway—one of top 3 pathways associated with BC | (133) |
| human patients | hypophysectomy | high rate of remission | (134, 141, 142) |
| BC cell lines | autocrine GH | increases proliferation | (146, 156, 158) |
| MCF7 cell line | autocrine GH | inhibits growth suppressors | (184) |
| MCF7 cell line | autocrine GH | resistance to chemotherapy (doxorubicin) induced apoptosis | (185) |
| MCF7 cell line | autocrine GH | increases DDR and resistance to starvation induced apoptosis | (156, 157, 186) |
| MCF7-hGH cells | GHRA (B2036) treatment | increases starvation induced apoptosis | (157) |
| BC cells | autocrine GH | resistance to starvation induced apoptosis | (187) |
| BC cells | autocrine GH | resistance to radiotherapy induced apoptosis | (188) |
| BC cells | autocrine GH | resistance to chemotherapy (MMC, doxorubicin, cisplatin) induced apoptosis | (162, 189) |
| BC cells | autocrine GH | resistance to oxidative stress induced apoptosis | (190) |
| ER+ and TNBC cells | autocrine GH | resistance to chemotherapy (MMC) induced apoptosis | (162) |
| ER+ and TNBC cells | autocrine GH + GHRA (B2036) treatment | sensitized to radiotherapy induced apoptosis | (188) |
| ER+ and TNBC cells | exogenous GH + GHRA (pegvisomant) treatment | sensitized to chemotherapy (doxorubicin) induced apoptosis | (160, 163) |
| patient-derived primary cells | anti-GHR shRNA | decreases cell viability, drug efflux, sensitized to chemotherapy (docetaxel) induced apoptosis | (145) |
| multiple BC cell types | autocrine GH | induces EMT, promotes migration-invasion | (36, 159, 161, 168) |
| BC cell line | autocrine GH | promotes DNA methylation, EMT induction | (191) |
| multiple BC cell types | orthotopic xenograft—nude mice | EMT induction, metastasis, ECM remodeling, stromal fibrosis | (36, 159, 161) |
| ER− BC cell xenograft in nude mice | autocrine GH | higher rate of invasion and metastases | (162, 188) |
| nude mouse xenograft | GHRA (B2036) treatment | sensitized to MMC induced apoptosis | (162) |
| T47D xenografts—nude mice | treated with GH | tumor proliferation, potentiation of estrogen effect | (192, 193) |
| TNBC cell lines | autocrine GH | resistance to tamoxifen, curcumin induced apoptosis | (164, 165) |
| estradiol-treated parous rats + MNU | increased serum GH | increased rate of tumorigenesis | (180) |
| control vs SDR | DMBA or MNU treatment | lower tumor incidence and size in SDR | (194) |
| SDR + GH | DMBA treatment | increased tumor incidence | (195, 196) |
| tumor bearing SDR + GH | GH withdrawal | tumor regression | (197) |
| SDR + GH + doxorubicin | GH withdrawal | sensitized to doxorubicin induced apoptosis | (198) |
| hGH/bGH transgenic mice | changes in mammary tissue | neoplasia (only for hGH transgenic, not oGH or bGH) | (155) |
| C3(1)/Tag mice | crossed with GHRKO mice | GHRKO-Tag mice—suppressed tumor incidence and tumor size | (199) |
| C3(1)/Tag mice | crossed with inducible-GHRKO mice | ind-GHRKO-Tag mice—tumor growth regression | (200) |
| DMBA treatment | GHA vs control mice | lower tumor incidence, size, and burden | (201) |
| DMBA treatment | AOiGHD vs control mice | lower tumor incidence, size, and burden | (202) |
| MCF7 xenograft in nude mice | GHRA (pegvisomant) treatment | reduced proliferation, increased apoptosis, reduced tumor growth | (162, 163, 203) |
| ER− primary cell xenograft in nude mice | GHR knockdown cells | reduced tumor growth, sensitized to docetaxel induced apoptosis | (145) |
| Material . | Method . | Study summary . | Reference . |
|---|---|---|---|
| normal mammary epithelial cell | autocrine GH | oncogenic transformation and in vivo tumor growth | (32, 154, 155) |
| BC cell lines, patient samples | RNA and protein | GH and GHR expression | (21, 35, 56, 143-146, 150-153) |
| patient samples | IHC for GHR | enriched in ER− BC samples | (145) |
| patient samples | IHC for GH, clinical correlation | GH overexpression in cancer tissue, correlates with poorer survival | (183) |
| patient sample | protein expression | tumor GHR expression correlates with aggressive metastasis | (144) |
| patient sample—IHC | correlation with tumor GH expression | tumor GH expression correlates with lymph node metastasis, tumor grade | (183) |
| autocrine GH in cell line, patient sample-RNA | RNA expression | autocrine GH expression intact in metastatic tumors | (35, 36) |
| patient data | GWAS data analyses | GH signaling pathway—one of top 3 pathways associated with BC | (133) |
| human patients | hypophysectomy | high rate of remission | (134, 141, 142) |
| BC cell lines | autocrine GH | increases proliferation | (146, 156, 158) |
| MCF7 cell line | autocrine GH | inhibits growth suppressors | (184) |
| MCF7 cell line | autocrine GH | resistance to chemotherapy (doxorubicin) induced apoptosis | (185) |
| MCF7 cell line | autocrine GH | increases DDR and resistance to starvation induced apoptosis | (156, 157, 186) |
| MCF7-hGH cells | GHRA (B2036) treatment | increases starvation induced apoptosis | (157) |
| BC cells | autocrine GH | resistance to starvation induced apoptosis | (187) |
| BC cells | autocrine GH | resistance to radiotherapy induced apoptosis | (188) |
| BC cells | autocrine GH | resistance to chemotherapy (MMC, doxorubicin, cisplatin) induced apoptosis | (162, 189) |
| BC cells | autocrine GH | resistance to oxidative stress induced apoptosis | (190) |
| ER+ and TNBC cells | autocrine GH | resistance to chemotherapy (MMC) induced apoptosis | (162) |
| ER+ and TNBC cells | autocrine GH + GHRA (B2036) treatment | sensitized to radiotherapy induced apoptosis | (188) |
| ER+ and TNBC cells | exogenous GH + GHRA (pegvisomant) treatment | sensitized to chemotherapy (doxorubicin) induced apoptosis | (160, 163) |
| patient-derived primary cells | anti-GHR shRNA | decreases cell viability, drug efflux, sensitized to chemotherapy (docetaxel) induced apoptosis | (145) |
| multiple BC cell types | autocrine GH | induces EMT, promotes migration-invasion | (36, 159, 161, 168) |
| BC cell line | autocrine GH | promotes DNA methylation, EMT induction | (191) |
| multiple BC cell types | orthotopic xenograft—nude mice | EMT induction, metastasis, ECM remodeling, stromal fibrosis | (36, 159, 161) |
| ER− BC cell xenograft in nude mice | autocrine GH | higher rate of invasion and metastases | (162, 188) |
| nude mouse xenograft | GHRA (B2036) treatment | sensitized to MMC induced apoptosis | (162) |
| T47D xenografts—nude mice | treated with GH | tumor proliferation, potentiation of estrogen effect | (192, 193) |
| TNBC cell lines | autocrine GH | resistance to tamoxifen, curcumin induced apoptosis | (164, 165) |
| estradiol-treated parous rats + MNU | increased serum GH | increased rate of tumorigenesis | (180) |
| control vs SDR | DMBA or MNU treatment | lower tumor incidence and size in SDR | (194) |
| SDR + GH | DMBA treatment | increased tumor incidence | (195, 196) |
| tumor bearing SDR + GH | GH withdrawal | tumor regression | (197) |
| SDR + GH + doxorubicin | GH withdrawal | sensitized to doxorubicin induced apoptosis | (198) |
| hGH/bGH transgenic mice | changes in mammary tissue | neoplasia (only for hGH transgenic, not oGH or bGH) | (155) |
| C3(1)/Tag mice | crossed with GHRKO mice | GHRKO-Tag mice—suppressed tumor incidence and tumor size | (199) |
| C3(1)/Tag mice | crossed with inducible-GHRKO mice | ind-GHRKO-Tag mice—tumor growth regression | (200) |
| DMBA treatment | GHA vs control mice | lower tumor incidence, size, and burden | (201) |
| DMBA treatment | AOiGHD vs control mice | lower tumor incidence, size, and burden | (202) |
| MCF7 xenograft in nude mice | GHRA (pegvisomant) treatment | reduced proliferation, increased apoptosis, reduced tumor growth | (162, 163, 203) |
| ER− primary cell xenograft in nude mice | GHR knockdown cells | reduced tumor growth, sensitized to docetaxel induced apoptosis | (145) |
Abbreviations: AOiGHD, adult-onset isolated growth hormone deficiency; BC, breast cancer; DDR, DNA damage repair; DMBA, dimethylbenzanthracene; ECM, extracellular matrix; EMT, epithelial-to-mesenchymal transition; ER, estrogen receptor; GH, growth hormone; GHA mice, mice transgenic for growth hormone receptor antagonist; GHR, growth hormone receptor; GHRA, growth hormone receptor antagonist; GWAS, genome-wide association study; IHC, immunohistochemistry; MMC, mitomycin C; MNU, N-methyl-N-nitrosourea; SDR, Sprague Dawley rats; TNBC, triple-negative breast cancer.
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