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

I. Screpanti, M. P. Felli, E. Toniato, D. Meco, S. Martinotti, L. Frati, A. Santoni, A. Gulino

Research output: Contribution to journalArticle

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 non-adherent 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.

Original languageEnglish
Pages (from-to)445-449
Number of pages5
JournalInternational Journal of Cancer
Volume47
Issue number3
Publication statusPublished - 1991

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Screpanti, I., Felli, M. P., Toniato, E., Meco, D., Martinotti, S., Frati, L., Santoni, A., & Gulino, A. (1991). Enhancement of natural-killer-cell susceptibility of human breast-cancer cells by estradiol and v-Ha-ras oncogene. International Journal of Cancer, 47(3), 445-449.