The role of the estrogen receptor in tumor progression.
We will discuss two estrogen receptor (ER) variants that may play a role in breast cancer initiation or progression. One is a truncated receptor, which has been named the exon 5 ER deletion variant, and the other is called a hyper-sensitive variant of the ER that is sensitive to low levels of hormone. Both ER variants differ from the wild-type ER in their hormone binding domains (HBD). The exon 5 ER deletion variant lacks a large portion of the HBD, while the hyper-sensitive ER variant has a point mutation in a conserved region of the HBD. The exon 5 ER deletion variant is transcriptionally active in the absence of hormone, and is thus considered constitutively-active. In contrast, the hyper-sensitive ER variant is functionally active in response to subphysiological concentrations of estrogen. We speculate that both ER variants may form productive heterodimers with wild-type receptor to modify the normal function of ER in the breast.
Lemieux
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Department of Medicine, Division of Medical Oncology, The University of Texas, Health Science Center at San Antonio, TX 78284-7884, USA.
Fuqua
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D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D006224:Cricetinae; D018450:Disease Progression; D004967:Estrogens / Q000502:physiology; D005091:Exons / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D046911:Macromolecular Substances; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D055503:Protein Multimerization; D011506:Proteins / Q000378:metabolism; D012326:RNA Splicing; D011960:Receptors, Estrogen / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D012045:Regulatory Sequences, Nucleic Acid
D004967:Estrogens; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D011506:Proteins; D011960:Receptors, Estrogen