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Progesterone receptors in breast cancer

  • Chapter
Genes, Oncogenes, and Hormones

Part of the book series: Cancer Treatment and Research ((CTAR,volume 61))

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Abstract

Steroid hormone receptors are members of a gene family of liganddependent transcriptional activators that also includes receptors for vitamin D, thyroid hormone, retinoic acid, and a number of transcriptional activators with as yet unknown ligands. Cloning of receptor genes and mutagenesis studies have revealed that steroid receptors are modular proteins organized into the functional domains shown in Figure 1. A highly conserved DNA binding domain (region C) located in the central portion of the molecule contains two zinc finger structures. The carboxyl terminal region (E) harbors domains for steroid binding and receptor dimerization. The amino terminus (A/B) is highly variable, both with respect to amino acid sequence and length, and is important for maximal transcriptional activity [1–4]. The progesterone receptor (PR) in breast cancer cells and in several normal reproductive tissues is produced as two steroid-binding proteins of different lengths, termed PR-A and PR-B [5, 6]. The two proteins arise from a single gene either by initiation of translation at two different start sites within the same RNA transcript or from separate mRNAs produced by the use of alternate promoters [7–9]. PR-A is a truncated version of PR-B, missing 165 amino acids present in the N terminus of PR-B (Figure 1). The two PR forms, therefore, are identical in sequence in their hormone and DNA binding domains. In human breast cancer cells, PR-A and PR-B have apparent molecular weights of ≈94,000 and ≈120,000 respectively [6]. This property of the progesterone receptor is unique among the sex steroid and glucocorticoid receptors. Receptors for estrogen (ER), androgens (AR), and glucocorticoids (GR) are all synthesized as single-sized proteins. The functional role of PR-A and PR-B are not known. They have been reported to exhibit some differences in target gene specificities, suggesting that expression of two PR forms from the same gene may provide a mechanism to expand functional diversity [10].

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Authors
  1. Candace A. Beck
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  2. Dean P. Edwards
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  1. Lombardi Cancer Research Center, Georgetown University School of Medicine, Washington, D.C., USA

    Robert B. Dickson  & Marc E. Lippman  & 

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Beck, C.A., Edwards, D.P. (1991). Progesterone receptors in breast cancer. In: Dickson, R.B., Lippman, M.E. (eds) Genes, Oncogenes, and Hormones. Cancer Treatment and Research, vol 61. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3500-3_16

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