Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This minireview summarizes the role that progesterone (P4) plays in regulating granulosa and luteal cell function. These actions include the stimulation of P4 synthesis and the inhibition of estrogen synthesis, mitosis, and apoptosis. P4 also plays a key role in the ovulatory process. Although P4's actions are well documented, the mechanism or mechanisms that mediate all of these actions have not been defined. In addition to P4-induced gene transcription that is mediated by the nuclear P4 receptors (PGR-A and PGR-B), three other receptor/signal transduction pathways could account for P4's intraovarian actions. These pathways could be mediated by 1) the PGR localizing at or near the plasma membrane and activating SRC family kinases, 2) a membrane progestin receptor that responds to P4 by lowering intracellular cAMP and increasing MAPK 3/1 activity, and 3) a membrane receptor complex composed of serpine 1 mRNA binding protein (also known as PAIRBP1 or RDA288) and progesterone receptor membrane component 1. Ligand activation of this complex likely leads to an increase in protein kinase G activity, the maintenance of low basal intracellular free calcium, and the inhibition of granulosa and luteal cell mitosis and apoptosis. Given the complexity of P4's actions within the ovary, it is likely that all of these receptor/signal transduction pathways influence some aspect of ovarian function with the specific P4 response dependent on 1) the expression pattern of these putative P4 receptors, 2) the P4 binding affinity of each receptor system, and 3) the amount of available P4.
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PMID:Multiplicity of progesterone's actions and receptors in the mammalian ovary. 1645 58

Breast cancer is the most common and molecularly relatively well characterized malignant disease in women, however, its progression to metastatic cancer remains lethal for 78% of patients 5years after diagnosis. Novel markers could identify the high risk patients and their verification using quantitative methods is essential to overcome genetic, inter-tumor and intra-tumor variability and translate novel findings into cancer diagnosis and treatment. We recently identified 13 proteins associated with estrogen receptor, tumor grade and lymph node status, the key factors of breast cancer aggressiveness, using untargeted proteomics. Here we verified these findings in the same set of 96 tumors using targeted proteomics based on selected reaction monitoring with mTRAQ labeling (mTRAQ-SRM), transcriptomics and immunohistochemistry and validated in 5 independent sets of 715 patients using transcriptomics. We confirmed: (i) positive association of anterior gradient protein 2 homolog (AGR2) and periostin (POSTN) and negative association of annexin A1 (ANXA1) with estrogen receptor status; (ii) positive association of stathmin (STMN1), cofilin-1 (COF1), plasminogen activator inhibitor 1 RNA-binding protein (PAIRBP1) and negative associations of thrombospondin-2 (TSP2) and POSTN levels with tumor grade; and (iii) positive association of POSTN, alpha-actinin-4 (ACTN4) and STMN1 with lymph node status. This study highlights a panel of gene products that can contribute to breast cancer aggressiveness and metastasis, the understanding of which is important for development of more precise breast cancer treatment.
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PMID:Targeted proteomics driven verification of biomarker candidates associated with breast cancer aggressiveness. 2821 24