The influence of inflammatory cytokines on estrogen production and cell proliferation in human breast cancer cells.
Estrogens play important roles in the development of breast cancer. Inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-1 beta (IL-1 beta) exist at high concentrations in breast cancer tissue. Although these cytokines are thought to exert some effect on cancer growth, their precise mechanism is still unclear. In the present study, we investigated the effects of inflammatory cytokines on aromatase (Arom) and steroid sulfatase (STS), which are estrogen-producing enzymes, and cell proliferation using human breast cancer cell lines (SK-BR-3, MCF-7). IL-6 and IL-1 beta stimulated the activity of Arom and STS. Estrone sulfate (E1-S) had a stimulus effect on cell proliferation of MCF-7. Although IL-6 did not show significant effect on cell proliferation, cell proliferation was significantly increased when IL-6 and E1-S were simultaneously added to the incubation medium. This cell proliferative effect was apparently stronger than the addition of E1-S alone. Addition of IL-1 beta in the presence of E1-S also significantly enhanced cell proliferation though IL-1 beta alone did not show any effect. These results led us to the hypothesis that inflammatory cytokines such as IL-6 and IL-1 beta regulate proliferation of breast cancer cells through estrogen production by steroid-catalyzing enzymes in the tissue.
Department of Obstetrics and Gynecology, Showa University School of Medicine, Shinagawa-ku, Tokyo 142-8666, Japan.
Susumu
S
Honma
Kazuhisa
K
Shimodaira
Yukiko
Y
Shimizu
Naoko
N
Tsuchiya
Hiroshi
H
Saito
Takumi
T
Yanaihara
Takashi
T
Okai
D001141:Aromatase / Q000378:metabolism; D001192:Arylsulfatases / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004967:Estrogens / Q000096:biosynthesis*; D004970:Estrone / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D012795:Sialoglycoproteins / Q000494:pharmacology*; D043266:Steryl-Sulfatase; D013451:Sulfonic Acids / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004967:Estrogens; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D012795:Sialoglycoproteins; D013451:Sulfonic Acids; D004970:Estrone; D001141:Aromatase; D001192:Arylsulfatases; D043266:Steryl-Sulfatase; C017296:estrone sulfate