Enhancement of natural-killer-cell susceptibility of human breast-cancer cells by estradiol and v-Ha-ras oncogene.
Natural killer (NK) cells are putative components of the cellular immune response to transformed cells. Since both estradiol treatment and ras-oncogene overexpression enhance tumorigenicity of hormone-dependent breast-cancer cells, we studied the effects of estrogen and of the activated v-Ha-ras oncogene on NK susceptibility of MCF-7 human breast-cancer cells. MCF-7 cells were sensitive to cytolysis mediated by resting and IL2-activated peripheral-blood non-adherent lymphocytes. Lysis appeared to be mediated by NK cells, since it was abrogated by treatment of effector cells with alpha-CD16 monoclonal antibody (MAb) plus complement (c'). Estradiol treatment of MCF-7 cells was able to significantly increase their sensitivity to the lysis by IL2-activated and unactivated peripheral-blood lymphocytes, as early as 24 hr throughout 10 days of hormone treatment. Hormone-insensitive, estrogen-receptor-negative breast-cancer cells (BT20) did not change their NK susceptibility after estradiol treatment. Increased NK susceptibility was also observed in v-Ha-ras-transfected and oncogene product overexpressing MCF-7 cells (MCF-7-ras) with respect to cells transfected with the selectable gene marker gpt alone (MCF-7-gpt). Overexpression of v-Ha-ras appeared to be able to bypass the need for estrogen to increase NK susceptibility, since estradiol-treated MCF-7-ras cells were not lysed more than untreated MCF-7-ras cells. The enhancement of NK susceptibility observed after both estradiol treatment and v-Ha-ras overexpression suggests that the hormone-mediated and the ras-oncogene-mediated signalling systems share events involved in the control of tumor-cell/host-effector-cell interactions.
Screpanti
I
I
Department of Experimental Medicine, University La Sapienza, Rome, Italy.
Felli
M P
MP
Toniato
E
E
Meco
D
D
Martinotti
S
S
Frati
L
L
Santoni
A
A
Gulino
A
A
D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D011905:Genes, ras / Q000502:physiology*; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000502:physiology*; D009857:Oncogenes / Q000502:physiology*; D014407:Tumor Cells, Cultured
D004958:Estradiol