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 E2 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-alpha, TGF-alpha, EGF, and TGF-beta, in cancer tissue specimens from these three different groups. In MCF-7 showing an E2-stimulative response, the expression of mRNAs of both TNF-alpha and TGF-alpha were suppressed by 10(-2) nM E2, but these same expressions in KSE-1 showing an E2 stimulative response were enhanced by E2. The mRNA expression of TGF-beta in these two cell lines was suppressed by 10(-2) nM E2, but that of EGF was enhanced. In clinical cases showing an E2-inhibitive response, the mRNA expression ratio of TNF-alpha/TGF-beta was above 2.5, but under 2.5 in E2-uninhibitive response cases. The mRNA expression ratio of TGF-alpha/TGF-beta was over 1.8 in the E2-inhibitive responsive cases, but under 1.8 in the E2-uninhibitive response cases. The mRNA expression ratio of EGF/TGF-beta did not show any regular tendency in three groups showing a different E2-response in vitro. Based on in vitro results and mRNA expression in clinical cases, the cytokine expression for E2-inhibitive cancer cells differed from those of E2-stimulative and -insensitive cells. Therefore, E2-inhibitive cancer cells are thus considered to possibly possess a characteristic growth regulation which is different from that for E2-uninhibitive cancer cells.