Enhancement of natural‐killer‐cell susceptibility of human breast‐cancer cells by estradiol and v‐Ha‐ras Oncogene

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Abstract
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 nonadherent lymphocytes. Lysis appeared to be mediated by NK cells, since it was abrogated by treatment of effector cells with α‐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.