Steroid hormone receptor signaling in tumorigenesis.
Excessive activation of the hormone signaling pathways is implicated in several disorders of the target tissues, with cancer being one of the most serious fallouts. Steroid hormone receptors are key proteins through which steroid hormones convey their signals to the cells. Deregulated activity of the hormone receptors due to their altered activation; stability or sub-cellular localization is heavily implicated in the onset and progress of cancers. The role played by estrogen and its receptors in breast cancer remains the most thoroughly investigated steroid-dependent cancer system till date. Choosing it as an example, we have summarized the molecular mechanisms underlying the action of the estrogen receptors (ERs) in manifesting the effects of the estrogens in the cells. A special emphasis is placed on the molecular mechanism of their functionality, role of the coactivator proteins, and the reasons for the deregulated signaling. The therapeutic approaches resulting from the mechanistic study of the ER action and their efficacies are also discussed.
Singh
Rajesh R
RR
The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Kumar
Rakesh
R
D000818:Animals; D056970:Co-Repressor Proteins; D051548:Histone Acetyltransferases; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D056920:Nuclear Receptor Coactivator 1; D011960:Receptors, Estrogen / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013256:Steroids / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D056970:Co-Repressor Proteins; C438485:PELP1 protein, human; D011960:Receptors, Estrogen; D011987:Receptors, Steroid; D013256:Steroids; D015534:Trans-Activators; D014157:Transcription Factors; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1