Growth regulation by estradiol, progesterone and recombinant human epidermal growth factor of human breast carcinoma xenografts grown serially in nude mice.
Four human breast carcinoma xenografts, MCF-7, Br-10, T-61 and MX-1, were transplanted into female nude mice with or without pretreatment with estradiol and progesterone. Hormone receptors including cytosol and nuclear estrogen receptor (ERc and ERn) and progesterone receptor (PgR) were assessed by the dextran-coated charcoal method and exchange assay; epidermal growth factor receptor (EGFR) was measured by the 125I-EGF binding assay. MCF-7 and T-61 were ERc-, ERn- and PgR- positive, but Br-10 was positive only for ERc; MX-1 was negative for these hormone receptors, but was the only xenograft showing EGFR. The growth of MCF-7 and Br-10 was enhanced by exogenous estradiol and progesterone, whereas the growth of T-61 was markedly inhibited by exogenous estradiol; the growth of MX-1 was not influenced by these sex steroids. Recombinant human epidermal growth factor (rhEGF) inhibited the growth of EGFR-positive MX-1 dose-dependently, whereas no changes were observed in the growth of EGFR-negative MCF-7, Br-10 and T-61 after treatment with rhEGF. This paradoxical inhibition of rhEGF on EGFR-positive MX-1 might be due to down-regulation of EGFR, as shown in the ER-positive xenograft T-61, whose growth was inhibited by estradiol.
Kubota
T
T
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
Josui
K
K
Fukutomi
T
T
Kitajima
M
M
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000032:analysis; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011374:Progesterone / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D014183:Transplantation, Heterologous
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011994:Recombinant Proteins; D011374:Progesterone; D004958:Estradiol; D004815:Epidermal Growth Factor; D066246:ErbB Receptors