Isoform specificity of progesterone receptor antibodies

Fabris, Victoria; Abascal, María F.; Giulianelli, Sebastián; May, María; Sequeira, Gonzalo R.; Jacobsen, Britta M.; Lombès, Marc; Han, Julie; Tran, Luan H.; Molinolo, Alfredo A.; Lanari, Claudia

doi:10.1002/cjp2.83

Cited by 16 publications

(11 citation statements)

References 22 publications

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“…Thus, it is true that a subset of PR monoclonal antibodies recognizes only the PR-A isoform in archival FFPE tissue (14). Additionally, PR monoclonal antibodies may preferentially recognize PR-A isoforms (15,16) and weakly recognize selected post-translationally modified PR isoforms in archival formalinfixed paraffin-embedded (FFPE) breast cancer tissues (CA Lange, unpublished results).…”

Section: Pr Isoformsmentioning

confidence: 99%

Progesterone and Breast Cancer: an NCI Workshop Report

Sathyamoorthy

Lange

2020

HORM CANC

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Section: Pr Isoformsmentioning

confidence: 99%

Progesterone and Breast Cancer: an NCI Workshop Report

Sathyamoorthy

Lange

2020

HORM CANC

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“…The authors propose this assay to select patients with aggregated PR expression as candidates for an antiprogestin treatment. As mentioned before, the specificity of the PRA antibody has not been corroborated (Fabris et al 2017).…”

Section: Pr Isoforms In Breast Cancer Cohortsmentioning

confidence: 85%

“…Following these assumptions, many investigators have published results describing and quantifying PR isoform expression in different tissues using IHC (Kreizman-Shefer et al 2014, Bartosch et al 2015, Bonneterre et al 2016. In xenografts, using cell lines modified to express either PRA or PRB, this antibody proved to be excellent to recognize both PR isoforms by IHC (Fabris et al 2017).…”

Section: Methods To Determine Pr Isoform Expressionmentioning

confidence: 99%

“…In addition, tamoxifen, but not anastrozole-treated patients had a significantly shorter time to distant relapse if their tumors had high mean PRA/PRB ratios, suggesting that the PRA/PRB ratio may be a discriminating factor in predicting response to these endocrine agents. The major drawback in this study is that the NCL-PGR-312 antibody used to detect PRA recognizes both PR isoforms in human xenografts (Fabris et al 2017). Bonnaterre and coworkers reported a novel immunohistochemical analysis to distinguish tumors in which PR is activated (Bonneterre et al 2016).…”

Section: Pr Isoforms In Breast Cancer Cohortsmentioning

confidence: 97%

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Biological and clinical impact of imbalanced progesterone receptor isoform ratios in breast cancer

Lamb¹,

Fabris²,

Jacobsen

et al. 2018

Endocrine-Related Cancer

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There is a consensus that progestins and thus their cognate receptor molecules, the progesterone receptors (PR), are essential in the development of the adult mammary gland and regulators of proliferation and lactation. However, a role for natural progestins in breast carcinogenesis remains poorly understood. A hint to that possible role came from studies in which the synthetic progestin medroxyprogesterone acetate was associated with an increased breast cancer risk in women under hormone replacement therapy. However, progestins have been also used for breast cancer treatment and to inhibit the growth of several experimental breast cancer models. More recently, PR have been shown to be regulators of estrogen receptor signaling. With all this information, the question is how can we target PR, and if so, which patients may benefit from such an approach? PR are not single unique molecules. Two main PR isoforms have been characterized, PRA and PRB, that exert different functions and the relative abundance of one isoform respect to the other determines the response of PR agonists and antagonists. Immunohistochemistry with standard antibodies against PR do not discriminate between isoforms. In this review, we summarize the current knowledge on the expression of both PR isoforms in mammary glands, in experimental models of breast cancer and in breast cancer patients, to better understand how the PRA/PRB ratio can be exploited therapeutically to design personalized therapeutic strategies.

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“…The expression of the PGR gene is controlled by two promotors to produce the main mRNA transcripts, which encode the classical PRs PR‐A and PR‐B (Patel et al, ). Both receptors are similar, except that PR‐A lacks 164 amino acids at the N‐terminus (Fabris et al, ). In the nervous system, these classical PRs are localized in the cytoplasm.…”

Section: Progesterone and Prsmentioning

confidence: 99%

Progesterone Effects in the Nervous System

Theis

Theiß

2019

The Anatomical Record

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The sex hormone progesterone is mainly known as a key factor in establishing and maintaining pregnancy. In addition, progesterone has been shown to induce morphological changes in the central and peripheral nervous system by increasing dendrito-, spino-, and synaptogenesis in Purkinje cells (Wessel et al.: Cell Mol Life Sci (2014a) 1723-1740 and increasing axonal outgrowth in dorsal root ganglia (Olbrich et al.: Endocrinology (2013) 3784-3795). These effects mediated mainly by the classical progesterone receptors (PRs) A and B seem to be limited to young neurons. It may be assumed that microRNAs (miRNAs), which are potent regulators of nervous system maturation and degeneration, are also involved in the regulation of progesterone-mediated neuronal plasticity by altering the expression patterns of the corresponding PR A/B receptors (Theis and Theiss: Neural Regen Res (2015) 547-549, Pieczora et al.: Cerebellum (2017) 376-387). This review critically discusses current data on the neuroprotective effect of progesterone and its corresponding receptors in the nervous system, with possible regulatory processes by miRNAs. Preclinical studies on stroke and traumatic brain injury revealed neuroprotective and neuroregenerative effects of progesterone in the treatment of severe neurological diseases in animal models, but have so far failed in humans. In this context, the identification of specific miRNAs that regulate the expression of progesterone and PR could help to exploit the neuroprotective potential of progesterone for the treatment of various neurological disorders. The human nervous system is a highly complex tissue composed of neurons and glial cells with a limited ability to regenerate after lesion or degeneration. In particular, the loss of neurons, for example, due to aging processes, stroke, or traumatic brain injury (TBI), is mostly irreversible. The function of the degenerating neurons can be partially compensated by neighboring neurons, but astroglial-fibrotic scar formation minimizes neuronal regeneration .Progesterone, a sexual hormone, is mainly known for its key role in the female reproductive circuit and the maintenance of pregnancy. In this context, the fact that progesterone is also expressed in the male organism is often neglected (Schumacher et al., 2014). Besides this, Abbreviations: BBB = blood brain barrier; CNS = central nervous system; DRG = dorsal root ganglia; GABA = Gamma-amino butyric acid; miRNA = microRNA; NMDAR = N-Methyl-D-aspartate receptor; PC = Purkinje cells; PGRMC1 = progesterone receptor membrane component 1; PNS = peripheral nervous system; PR = progesterone receptor; SCI = spinal cord injury; TBI = traumatic brain injury

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Isoform specificity of progesterone receptor antibodies

Cited by 16 publications

References 22 publications

Progesterone and Breast Cancer: an NCI Workshop Report

Progesterone and Breast Cancer: an NCI Workshop Report

Biological and clinical impact of imbalanced progesterone receptor isoform ratios in breast cancer

Progesterone Effects in the Nervous System

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