Abstract
Cytokines, such as IL-6 and tumor necrosis factor (TNF)-α, have an important role in regulating estrogen synthesis in peripheral tissues, including normal and malignant breast tissues. The activities of the aromatase, estradiol 17β-hydroxysteroid dehydrogenase and estrone sulfatase are all increased by IL-6 and TNF-α. Prostaglandin E2 may also be an important regulator of aromatase activity in breast tumors. Macrophages and lymphocytes, which invade many breast tumors, are thought to be an important source of factors that can stimulate estrogen synthesis in malignant breast tissues. The co-ordinated stimulation of the activities of the enzymes that are involved in estrogen synthesis offers an explanation for the high concentrations of estrogens that are present in breast tumors.
Highlights
Considerable advances have been made in recent years in understanding the genetics and molecular biology of breast cancer, but for women in most western countries, breast cancer still remains a major cause of death
The majority of breast tumors are initially dependent upon estrogen to support their growth, with the highest incidence of breast cancer occurring in postmenopausal women at a time when ovarian production of estrogens has ceased
In this paper we review the evidence implicating cytokines, and other factors, in regulating the activities of the enzymes that are involved in estrogen synthesis in breast tissues
Summary
Considerable advances have been made in recent years in understanding the genetics and molecular biology of breast cancer, but for women in most western countries, breast cancer still remains a major cause of death. IL-6 and TNF-α can stimulate the activities of all the enzymes involved in estrogen synthesis; PGE2 is important in regulating aromatase gene expression in malignant tissues (Fig. 1). Three enzyme complexes are involved in estrogen synthesis in breast tissues: (1) Aromatase (Arom) which converts androstenedione (A) to estrone (E1); (2) estrone sulfatase (E1-STS) which hydrolyses estrone sulfate (E1-S) to E1 and (3) estradiol-17βhydroxysteroid dehydrogenase (17β-HSD) Type 1 which reduces E1 to the biologically active estrogen, estradiol (E2). Aromatase gene expression is thought to be regulated to a greater extent by PI. and PII, expression of which is stimulated by cAMP and factors such as prostaglandin (PG) E2, which increase cAMP levels Cytokines such as IL-6 and TNF-α increase 17β-HSD Type 1 activity, while their effect on E1-STS activity may be indirect. As cytokine production is reduced in immunosuppressed women, this finding supports the concept that cytokines have an important role in breast cancer, possibly acting via stimulation of estrogen synthesis [39,40]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
