Effects of tamoxifen, medroxyprogesterone acetate and estradiol on tumor growth and oncogene expression in MCF-7 breast cancer cell line transplanted into nude mice.
The effects of three hormonal agents with a different mechanism of action (tamoxifen [TAM], medroxyprogesterone acetate [MPA] and estradiol [E2]) on tumor growth, differentiation and oncogene expression were evaluated using the estrogen-receptor positive human breast carcinoma cell line MCF-7 transplanted into nude mice. In MCF-7 tumors treated with E2, tumor incidence, mean weight of tumors, 3H-thymidine labelling index, differentiation antigen HMFGM (human milk-fat globule membrane) and ras p21, c-myc, neu oncogene products, the level was significantly increased. On the other hand MPA suppressed all of them. TAM increased the level of c-myc expression and HMFGM antigen, but suppressed the others. This evidence indicates that E2 induces both proliferation and differentiation of MCF-7 tumor cells. MPA suppresses both proliferation and differentiation, and TAM induces differentiation and suppresses proliferation.
Mizukami
Y
Y
Pathology Section, Kanazawa University Hospital, Japan.
Tajiri
K
K
Nonomura
A
A
Noguchi
M
M
Taniya
T
T
Koyasaki
N
N
Nakamura
S
S
Matsubara
F
F
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000473:pathology*; D008525:Medroxyprogesterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D017258:Medroxyprogesterone Acetate; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009857:Oncogenes; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis; D016283:Proto-Oncogene Proteins p21(ras) / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D013629:Tamoxifen / Q000494:pharmacology*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D016271:Proto-Oncogene Proteins c-myc; D011960:Receptors, Estrogen; D013629:Tamoxifen; D004958:Estradiol; D017258:Medroxyprogesterone Acetate; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D008525:Medroxyprogesterone