Local estrogen production from aromatase-mediated conversion of androgens is an
important mechanism of autocrine growth stimulation in hormone-dependent breast cancers. The
control mechanism of aromatase enzymatic activity in recent years has been demonstrated to be more
complex than previously identified. Indeed, it is well known that aromatase expression is regulated at
the transcriptional level through the alternative use of tissue-specific promoters, whereas it has
become clear that the activity of this enzyme is also controlled by post-transcriptional modifications,
such as phosphorylation processes. This paper presents a selective review of the novel findings in this
area showing phosphorylation/dephosphorylation of aromatase as a switch to rapidly modulate its enzymatic activity.
Particularly, we describe studies conducted in our laboratories, focusing on the role of estrogens in modulating aromatase
activity in estrogen-dependent breast cancer cells. Two separate mechanisms are described. First, 17β-estradiol (E2),
through c-Src kinase, is able to enhance tyrosine phosphorylation levels of aromatase protein and increases its enzymatic
activity and estrogen biosynthesis. Secondly, E2, through the activation of PI3K/Akt pathway, impairs the ability of the
tyrosine phosphatase PTP1B to dephosphorylate aromatase, resulting in a consequent enhanced phosphorylation and
activity of the aromatase protein itself. These new controls of aromatase function provide insights into the mechanisms
through which local estrogen production can be altered in breast cancer tissues. They also offer a vast array of possibilities
for identifying different cell signalings that should be targeted in novel therapeutic strategies for breast cancer treatment.