In vivo growth regulation by cytokine in breast cancer cells showing an estradiol-inhibitive response in vitro.

The rates of the stimulative, insensitive, and inhibitive responses to 10 -2 nM E 2 in sixty clinical breast cancer cases were 24.2%, 45.2%, and 30.6%, respectively. We then examined the expression of mRNAs of such cytokines as TNF-α, TGF-α, EGF, and TGF-β, in cancer tissue specimens from these three different groups. In MCF-7 showing an E 2 -stimulative response, the expression of mRNAs of both TNF-α and TGF-α were suppressed by 10 -2 nM E 2, but these same expressions in KSE-I showing an E 2 stimulative response were enhanced by E 2 . The mRNA expression of TGF-β in these two cell lines was suppressed by 10 -2 nM E 2, but that of EGF was enhanced. In clinical cases showing an E 2 -inhibitive response, the mRNA expression ratio of TNF-α/TGF-β was above 2.5, but under 2.5 in E 2- uninhibitive response cases. The mRNA expression ratio of TGF-α/TGF-β was over 1.8 inthe E 2 -inhibitive responsive cases, but under 1.8 in the E 2 -uninhibitive response cases. The mRNA expression ratio of EGF/TGF-β did not show any regular tendency in three groups showing a different E 2 -response in vitro. Based on in vitro results and mRNA expression in clinical cases, the cytokine expression for E 2 -inhibitive cancer cells differed from those of E 2 -stimulative and -insensitive cells. Therefore, E 2 -inhibitive cancer cells are thus considered to possibly possess a characteristic growth regulation which is different from that for E 2 -uninhibitive cancer cells.