Growth-promoting Functions Research Articles

Suppressive effects of Bacillus spp. on mycelia, apothecia and sclerotia formation of Sclerotinia sclerotiorum and potential as biological control of white mold on mustard

Biological control, especially with Bacillus-based biocontrol agents, offers an attractive alternative to synthetic pesticides for sustainable management of white mold disease caused by Sclerotinia sclerotiorum. In this study, eight effective Bacillus isolates were isolated from rhizospheric soil samples as potential bacterial biocontrol agents. Cultural, biochemical, and molecular analyses of 16S rDNA and gyrase subunit A (gyrA) confirmed that all isolates were identified as Bacillus amyloliquefaciens subsp. plantarum. The production of hydrolytic enzymes and the plant growth-promotional attributes of these isolates confirmed their multifaceted potential. Molecular analysis of the eight biosynthetic genes, which are related to antibiotic properties of bacilli, revealed that all of the isolates possess five genes: bacA for bacilysin, dfnM for difficidin, fenA for fengycin, ituA for iturin, and sfp for surfactin. The Bacillus isolates inhibited mycelial growth and suppressed formation of sclerotia during an in vitro test against S. sclerotiorum. Deformities and cell-wall lysis of mycelia, abnormalities of apothecia, and germination failure of ascospores through interaction with the Bacillus isolates were observed with light and scanning electron microscopes, suggesting that they have high antagonistic effects against S. sclerotiorum. Seed bacterization with the Bacillus isolates protected mustard seedlings in vitro up to 98 % against S. sclerotiorum. In a pot experiment, damages of mustard plants against the pathogen decreased up to 90 % after foliar spray of the Bacillus isolates. In addition, the isolates increased seed germination and accelerated seedling vigor of mustard, suggesting that they have plant growth-promoting functions.

Human Umbilical Tissue-Derived Cells Promote Synapse Formation and Neurite Outgrowth via Thrombospondin Family Proteins.

Human umbilical tissue-derived cells (hUTC) are currently under clinical investigation for the treatment of geographic atrophy secondary to age-related macular degeneration. These cells show great promise for the treatment of neurological disorders; however, the therapeutic effects of these cells on CNS neurons are not fully understood. Here we provide compelling evidence that hUTCs secrete multiple factors that work synergistically to enhance synapse formation and function, and support neuronal growth and survival. Moreover, we identified thrombospondins (TSPs) as the hUTC-secreted factors that mediate the synaptogenic and growth-promoting functions of these cells. Our findings highlight novel paracrine effects of hUTC on CNS neuron health and connectivity and begin to unravel potential therapeutic mechanisms by which these cells elicit their effects.

MITF and c-Jun antagonism interconnects melanoma dedifferentiation with pro-inflammatory cytokine responsiveness and myeloid cell recruitment.

Inflammation promotes phenotypic plasticity in melanoma, a source of non-genetic heterogeneity, but the molecular framework is poorly understood. Here we use functional genomic approaches and identify a reciprocal antagonism between the melanocyte lineage transcription factor MITF and c-Jun, which interconnects inflammation-induced dedifferentiation with pro-inflammatory cytokine responsiveness of melanoma cells favouring myeloid cell recruitment. We show that pro-inflammatory cytokines such as TNF-α instigate gradual suppression of MITF expression through c-Jun. MITF itself binds to the c-Jun regulatory genomic region and its reduction increases c-Jun expression that in turn amplifies TNF-stimulated cytokine expression with further MITF suppression. This feed-forward mechanism turns poor peak-like transcriptional responses to TNF-α into progressive and persistent cytokine and chemokine induction. Consistently, inflammatory MITFlow/c-Junhigh syngeneic mouse melanomas recruit myeloid immune cells into the tumour microenvironment as recapitulated by their human counterparts. Our study suggests myeloid cell-directed therapies may be useful for MITFlow/c-Junhigh melanomas to counteract their growth-promoting and immunosuppressive functions.

Paradox of plant growth promotion potential of rhizobacteria and their actual promotion effect on growth of barley (Hordeum vulgare L.) under salt stress

From the rhizosphere of two salt tolerant plant species, Hordeum secalinum and Plantago winteri growing in a naturally salt meadow, 100 strains were isolation on enrichment media for various plant growth-promoting (PGP) functions (ACC deaminase activity, auxin synthesis, calcium phosphate mobilization and nitrogen fixation). Based on the taxonomic affiliation of the isolated bacteria and their enrichment medium 22 isolates were selected to test their growth promotion effect on the crop barley (Hordeum vulgare) under salt stress in pot experiment. In parallel the isolates were characterized in pure culture for their plant growth-promoting activities. Surprisingly the best promotors did not display a promising set of PGP activities. Isolates with multiple PGP-activities in pure culture like Microbacterium natoriense strain E38 and Pseudomonas brassicacearum strain E8 did not promote plant growth. The most effective isolate was strain E108 identified as Curtobacterium flaccumfaciens, which increased barley growth up to 300%. In pure culture strain E108 showed only two out of six plant growth promoting activities and would have been neglected. Our results highlight that screening based on pure culture assays may not be suitable for recognition of best plant growth promotion candidates and could preclude the detection of both new PGPR and new plant promotion mechanisms.

The Cancer Genome Atlas Analysis Predicts MicroRNA for Targeting Cancer Growth and Vascularization in Glioblastoma

Using in silico analysis of The Cancer Genome Atlas (TCGA), we identified microRNAs associated with glioblastoma (GBM) survival, and predicted their functions in glioma growth and progression. Inhibition of two "risky" miRNAs, miR-148a and miR-31, in orthotopic xenograft GBM mouse models suppressed tumor growth and thereby prolonged animal survival. Intracranial tumors treated with uncomplexed miR-148a and miR-31 antagomirs exhibited reduced proliferation, stem cell depletion, and normalized tumor vasculature. Growth-promoting functions of these two miRNAs were, in part, mediated by the common target, the factor inhibiting hypoxia-inducible factor 1 (FIH1), and the downstream pathways involving hypoxia-inducible factor HIF1α and Notch signaling. Therefore, miR-31 and miR-148a regulate glioma growth by maintaining tumor stem cells and their niche, and providing the tumor a way to activate angiogenesis even in a normoxic environment. This is the first study that demonstrates intratumoral uptake and growth-inhibiting effects of uncomplexed antagomirs in orthotopic glioma.

Development of Resistance to EGFR-Targeted Therapy in Malignant Glioma Can Occur through EGFR-Dependent and -Independent Mechanisms.

Epidermal growth factor receptor (EGFR) is highly amplified, mutated, and overexpressed in human malignant gliomas. Despite its prevalence and growth-promoting functions, therapeutic strategies to inhibit EGFR kinase activity have not been translated into profound beneficial effects in glioma clinical trials. To determine the roles of oncogenic EGFR signaling in gliomagenesis and tumor maintenance, we generated a novel glioma mouse model driven by inducible expression of a mutant EGFR (EGFR*). Using combined genetic and pharmacologic interventions, we revealed that EGFR*-driven gliomas were insensitive to EGFR tyrosine kinase inhibitors, although they could efficiently inhibit EGFR* autophosphorylation in vitro and in vivo. This is in contrast with the genetic suppression of EGFR* induction that led to significant tumor regression and prolonged animal survival. However, despite their initial response to genetic EGFR* extinction, all tumors would relapse and propagate independent of EGFR*. We further showed that EGFR*-independent tumor cells existed prior to treatment and were responsible for relapse following genetic EGFR* suppression. And, the addition of a PI3K/mTOR inhibitor could significantly delay relapse and prolong animal survival. Our findings shed mechanistic insight into EGFR drug resistance in glioma and provide a platform to test therapies targeting aberrant EGFR signaling in this setting.

Prospects for the use of multi-component symbiotic systems of the Legumes

Legume-Rhizobial Symbiosis (LRS), Arbuscular Mycorrhiza (AM) and associations with Plant Growth-Promoting Bacteria (PGPB) implement nutritional and defensive functions in plant, improve soil fertility, and thus are appropriate to be used for sustainable crop production and soil restoration. Based on synergism and evolutional commonality of the symbioses, we propose a multi-component plant-microbe system with legume plant as a main component. Advances obtained from simultaneous inoculation of legumes with various beneficial microbes are summarized. Basic principles of legume breeding to improve effectiveness of interaction with a complex of the microbes along with problems and prospects for development of multi-microbial inoculants for legumes (and non-legumes) are stated.

Axon Regeneration Genes Identified by RNAi Screening inC. elegans

Axons of the mammalian CNS lose the ability to regenerate soon after development due to both an inhibitory CNS environment and the loss of cell-intrinsic factors necessary for regeneration. The complex molecular events required for robust regeneration of mature neurons are not fully understood, particularly in vivo. To identify genes affecting axon regeneration in Caenorhabditis elegans, we performed both an RNAi-based screen for defective motor axon regeneration in unc-70/β-spectrin mutants and a candidate gene screen. From these screens, we identified at least 50 conserved genes with growth-promoting or growth-inhibiting functions. Through our analysis of mutants, we shed new light on certain aspects of regeneration, including the role of β-spectrin and membrane dynamics, the antagonistic activity of MAP kinase signaling pathways, and the role of stress in promoting axon regeneration. Many gene candidates had not previously been associated with axon regeneration and implicate new pathways of interest for therapeutic intervention.

Steroidogenic Enzyme AKR1C3 Is a Novel Androgen Receptor-Selective Coactivator that Promotes Prostate Cancer Growth

Castration-resistant prostate cancer (CRPC) may occur by several mechanisms including the upregulation of androgen receptor (AR), coactivators, and steroidogenic enzymes, including aldo keto reductase 1C3 (AKR1C3). AKR1C3 converts weaker 17-keto androgenic precursors to more potent 17-hydroxy androgens and is consistently the major upregulated gene in CRPC. The studies in the manuscript were undertaken to examine the role of AKR1C3 in AR function and CRPC. LNCaP cells stably transfected with AKR1C3 and VCaP cells endogenously expressing AKR1C3 were used to understand the effect of AKR1C3 on prostate cancer cell and tumor growth in nude mice. Chromatin immunoprecipitation, confocal microscopy, and co-immunoprecipitation studies were used to understand the recruitment of AKR1C3, intracellular localization of AKR1C3 and its interaction with AR in cells, tumor xenograft, and in Gleason sum 7 CRPC tissues. Cells were transiently transfected for AR transactivation. Novel small-molecule AKR1C3-selective inhibitors were synthesized and characterized in androgen-dependent prostate cancer and CRPC models. We identified unique AR-selective coactivator- and prostate cancer growth-promoting roles for AKR1C3. AKR1C3 overexpression promotes the growth of both androgen-dependent prostate cancer and CRPC xenografts, with concomitant reactivation of androgen signaling. AKR1C3 interacted with AR in prostate cancer cells, xenografts, and in human CRPC samples and was recruited to the promoter of an androgen-responsive gene. The coactivator and growth-promoting functions of AKR1C3 were inhibited by an AKR1C3-selective competitive inhibitor. AKR1C3 is a novel AR-selective enzymatic coactivator and may represent the first of more than 200 known nuclear hormone receptor coactivators that can be pharmacologically targeted.

The C‐terminal cysteine of turbot Scophthalmus maximus translationally controlled tumour protein plays a key role in antioxidation and growth‐promoting functions

The translationally controlled tumour protein (TCTP) of turbot Scophthalmus maximus (SmTCTP) contains only one cysteine (Cys¹⁷⁰) at the C-terminal end. The biological role of this C-terminal Cys¹⁷⁰ in the antioxidation and growth-promoting functions of SmTCTP was examined by site-directed mutation of C170A (Cys¹⁷⁰ →Ala¹⁷⁰). It was found that C170A mutation not only obviously decreased the antioxidation capacity of the mutant-smtctp-transformed bacteria exposed to 0·22 mM hydrogen peroxide, but also significantly interrupted the normal growth and survival of the mutant-smtctp-transformed bacteria and flounder Paralichthys olivaceus gill (FG) cells, indicating a key role played by Cys¹⁷⁰ in the antioxidation and growth-promoting functions of SmTCTP. This study also suggested that the self-dimerization or dimerization with other interacting proteins is critical to the growth-promoting function of SmTCTP.

Androgen receptor functions in castration-resistant prostate cancer and mechanisms of resistance to new agents targeting the androgen axis.

The metabolic functions of androgen receptor (AR) in normal prostate are circumvented in prostate cancer (PCa) to drive tumor growth, and the AR also can acquire new growth-promoting functions during PCa development and progression through genetic and epigenetic mechanisms. Androgen deprivation therapy (ADT, surgical or medical castration) is the standard treatment for metastatic PCa, but patients invariably relapse despite castrate androgen levels (castration-resistant PCa, CRPC). Early studies from many groups had shown that AR was highly expressed and transcriptionally active in CRPC, and indicated that steroids from the adrenal glands were contributing to this AR activity. More recent studies showed that CRPC cells had increased expression of enzymes mediating androgen synthesis from adrenal steroids, and could synthesize androgens de novo from cholesterol. Phase III clinical trials showing a survival advantage in CRPC for treatment with abiraterone (inhibitor of the enzyme CYP17A1 required for androgen synthesis that markedly reduces androgens and precursor steroids) and for enzalutamide (new AR antagonist) have now confirmed that AR activity driven by residual androgens makes a major contribution to CRPC, and led to the recent Food and Drug Administration approval of both agents. Unfortunately, patients treated with these agents for advanced CRPC generally relapse within a year and AR appears to be active in the relapsed tumors, but the molecular mechanisms mediating intrinsic or acquired resistance to these AR-targeted therapies remain to be defined. This review outlines AR functions that contribute to PCa development and progression, the roles of intratumoral androgen synthesis and AR structural alterations in driving AR activity in CRPC, mechanisms of action for abiraterone and enzalutamide, and possible mechanisms of resistance to these agents.

EIF4E3 acts as a tumor suppressor by utilizing an atypical mode of methyl-7-guanosine cap recognition

Recognition of the methyl-7-guanosine (m(7)G) cap structure on mRNA is an essential feature of mRNA metabolism and thus gene expression. Eukaryotic translation initiation factor 4E (eIF4E) promotes translation, mRNA export, proliferation, and oncogenic transformation dependent on this cap-binding activity. eIF4E-cap recognition is mediated via complementary charge interactions of the positively charged m(7)G cap between the negative π-electron clouds from two aromatic residues. Here, we demonstrate that a variant subfamily, eIF4E3, specifically binds the m(7)G cap in the absence of an aromatic sandwich, using instead a different spatial arrangement of residues to provide the necessary electrostatic and van der Waals contacts. Contacts are much more extensive between eIF4E3-cap than other family members. Structural analyses of other cap-binding proteins indicate this recognition mode is atypical. We demonstrate that eIF4E3 relies on this cap-binding activity to act as a tumor suppressor, competing with the growth-promoting functions of eIF4E. In fact, reduced eIF4E3 in high eIF4E cancers suggests that eIF4E3 underlies a clinically relevant inhibitory mechanism that is lost in some malignancies. Taken together, there is more structural plasticity in cap recognition than previously thought, and this is physiologically relevant.

Nuclear IRS‐1 and cancer

The family of insulin receptor substrates (IRS) consists of four proteins (IRS-1-IRS-4), which were initially characterized as typical cytosolic adaptor proteins involved in insulin receptor (IR) and insulin-like growth factor I receptor (IGF-IR) signaling. The first cloned and characterized member of the IRS family, IRS-1, has a predicted molecular weight of 132 kDa, however, as a result of its extensive serine phosphorylation it separates on a SDS gel as a band of approximately 160-185 kDa. In addition to its metabolic and growth-promoting functions, IRS-1 is also suspected to play a role in malignant transformation. The mechanism by which IRS-1 supports tumor growth is not fully understood, and the argument that IRS-1 merely amplifies the signal from the IGF-1R and/or IR requires further investigation. Almost a decade ago, we reported the presence of nuclear IRS-1 in medulloblastoma clinical samples, which express viral oncoprotein, large T-antigen of human polyomavirus JC (JCV T-antigen). This first demonstration of nuclear IRS-1 was confirmed by several other laboratories. Nuclear IRS-1 was also detected by cells expressing the SV40 T-antigen, v-Src, in immortalized fibroblasts stimulated with IGF-I, in hepatocytes, 32D cells, and in an osteosarcoma cell line. More recently, nuclear IRS-1 was detected in breast cancer cells in association with estrogen receptor alpha (ERα), and in JC virus negative medulloblastoma cells expressing estrogen receptor beta (ERβ), further implicating nuclear IRS-1 in cellular transformation. Here, we discuss how nuclear IRS-1 acting on DNA repair fidelity, transcriptional activity, and cell growth can support tumor development and progression.

DNA damage induces the IL-6/STAT3 signaling pathway, which has anti-senescence and growth-promoting functions in human tumors

IL-6 is a multifunctional cytokine that is important for immune responses, cell survival, apoptosis, and proliferation. However, little is known about the correlation between the IL-6 signaling pathway and DNA damage in human tumors. The present study demonstrates the role of the IL-6/STAT3 signaling pathway in human tumor cells exposed to DNA damage. Tumor cells exposed to DNA damage increase the expression and secretion of IL-6 and the phosphorylation of JAK1 and STAT3. The activation of the JAK1–STAT3 signaling pathway is inhibited by knockdown of gp130 or neutralization of soluble IL-6, implying that DNA damage induces the phosphorylation of JAK1 and STAT3 by autocrine IL-6. Interestingly, inhibition of the IL-6/STAT3 signaling pathway impairs the growth of tumor cells exposed to DNA damage and results in the induction of senescence. Therefore, the present study suggests that IL-6 inhibits senescence but promotes the survival and proliferation of tumor cells exposed to DNA damage through the activation of the JAK1–STAT3 signaling pathway.

Disruption of a Nuclear NFATc2 Protein Stabilization Loop Confers Breast and Pancreatic Cancer Growth Suppression by Zoledronic Acid

The aminobisphosphonate zoledronic acid has elicited significant attention due to its remarkable anti-tumoral activity, although its detailed mechanism of action remains unclear. Here, we demonstrate the existence of a nuclear GSK-3β-NFATc2 stabilization pathway that promotes breast and pancreatic cancer growth in vitro and in vivo and serves as a bona fide target of zoledronic acid. Specifically, the serine/threonine kinase GSK-3β stabilizes nuclear NFATc2 through phosphorylation of the serine-rich SP2 domain, thus protecting the transcription factor from E3-ubiquitin ligase HDM2-mediated proteolysis. Zoledronic acid disrupts this NFATc2 stabilization pathway through two mechanisms, namely GSK-3β inhibition and induction of HDM2 activity. Upon nuclear accumulation, HDM2 targets unphosphorylated NFATc2 for ubiquitination at acceptor lysine residues Lys-684/Lys-897 and hence labels the factor for subsequent proteasomal degradation. Conversely, mutagenesis-induced constitutive serine phosphorylation (Ser-215, Ser-219, and Ser-223) of the SP2 domain prevents NFATc2 from HDM2-mediated ubiquitination and degradation and consequently rescues cancer cells from growth suppression by zoledronic acid. In conclusion, this study demonstrates a critical role of the GSK-3β-HDM2 signaling loop in the regulation of NFATc2 protein stability and growth promotion and suggests that double targeting of this pathway is responsible, at least to a significant part, for the potent and reliable anti-tumoral effects of zoledronic acid.

Solution Structure of the Guanine Nucleotide-binding STAS Domain of SLC26-related SulP Protein Rv1739c from Mycobacterium tuberculosis

The structure and intrinsic activities of conserved STAS domains of the ubiquitous SulP/SLC26 anion transporter superfamily have until recently remained unknown. Here we report the heteronuclear, multidimensional NMR spectroscopy solution structure of the STAS domain from the SulP/SLC26 putative anion transporter Rv1739c of Mycobacterium tuberculosis. The 0.87-Å root mean square deviation structure revealed a four-stranded β-sheet with five interspersed α-helices, resembling the anti-σ factor antagonist fold. Rv1739c STAS was shown to be a guanine nucleotide-binding protein, as revealed by nucleotide-dependent quench of intrinsic STAS fluorescence and photoaffinity labeling. NMR chemical shift perturbation analysis partnered with in silico docking calculations identified solvent-exposed STAS residues involved in nucleotide binding. Rv1739c STAS was not an in vitro substrate of mycobacterial kinases or anti-σ factors. These results demonstrate that Rv1739c STAS binds guanine nucleotides at physiological concentrations and undergoes a ligand-induced conformational change but, unlike anti-σ factor antagonists, may not mediate signals via phosphorylation.

STAT3 controls myeloid progenitor growth during emergency granulopoiesis

AbstractGranulocyte colony-stimulating factor (G-CSF) mediates “emergency” granulopoiesis during infection, a process that is mimicked by clinical G-CSF use, yet we understand little about the intracellular signaling cascades that control demand-driven neutrophil production. Using a murine model with conditional deletion of signal transducer and activator of transcription 3 (STAT3) in bone marrow, we investigated the cellular and molecular mechanisms of STAT3 function in the emergency granulopoiesis response to G-CSF administration or infection with Listeria monocytogenes, a pathogen that is restrained by G-CSF signaling in vivo. Our results show that STAT3 deficiency renders hematopoietic progenitor cells and myeloid precursors refractory to the growth-promoting functions of G-CSF or L monocytogenes infection. STAT3 is necessary for accelerating granulocyte cell-cycle progression and maturation in response to G-CSF. STAT3 directly controls G-CSF–dependent expression of CCAAT-enhancer-binding protein β (C/EBPβ), a crucial factor in the emergency granulopoiesis response. Moreover, STAT3 and C/EBPβ coregulate c-Myc through interactions with the c-myc promoter that control the duration of C/EBPα occupancy during demand-driven granulopoiesis. These results place STAT3 as an essential mediator of emergency granulopoiesis by its regulation of transcription factors that direct G-CSF–responsive myeloid progenitor expansion.

Non-Redundant Selector and Growth-Promoting Functions of Two Sister Genes, buttonhead and Sp1, in Drosophila Leg Development

The radically distinct morphologies of arthropod and tetrapod legs argue that these appendages do not share a common evolutionary origin. Yet, despite dramatic differences in morphology, it has been known for some time that transcription factors encoded by the Distalless (Dll)/Dlx gene family play a critical role in the development of both structures. Here we show that a second transcription factor family encoded by the Sp8 gene family, previously implicated in vertebrate limb development, also plays an early and fundamental role in arthropod leg development. By simultaneously removing the function of two Sp8 orthologs, buttonhead (btd) and Sp1, during Drosophila embryogenesis, we find that adult leg development is completely abolished. Remarkably, in the absence of these factors, transformations from ventral to dorsal appendage identities are observed, suggesting that adult dorsal fates become derepressed when ventral fates are eliminated. Further, we show that Sp1 plays a much more important role in ventral appendage specification than btd and that Sp1 lies genetically upstream of Dll. In addition to these selector-like gene functions, Sp1 and btd are also required during larval stages for the growth of the leg. Vertebrate Sp8 can rescue many of the functions of the Drosophila genes, arguing that these activities have been conserved, despite more than 500 million years of independent evolution. These observations suggest that an ancient Sp8/Dlx gene cassette was used in an early metazoan for primitive limb-like outgrowths and that this cassette was co-opted multiple times for appendage formation in multiple animal phyla.

MicroRNA-196a Is a Potential Marker of Progression during Barrett's Metaplasia-Dysplasia-Invasive Adenocarcinoma Sequence in Esophagus

Barrett's esophagus (BE)/Barrett's metaplasia (BM) is a recognized precursor of esophageal adenocarcinoma (EA) with an intermediary stage of dysplasia. The low yield and high cost of endoscopic screening of patients with BE underscores the need for novel biomarkers, such as microRNA (miRNA), which have emerged as important players in neoplastic progression for risk assessment of developing dysplasia/adenocarcinoma. Recently, we reported highly elevated levels of miRNA-196a (miR-196a) in EA and demonstrated its growth-promoting and anti-apoptotic functions. Here, we evaluated miR-196a as a marker of BE progression to low-grade dysplasia, high-grade dysplasia, and EA using microdissected paraffin-embedded tissues from 11 patients. Higher levels of miR-196a were observed in EA, BE, and dysplastic lesions compared with normal squamous mucosa, and in high-grade dysplasia compared with BE and low-grade dysplasia. Using frozen tumor tissues from 10 additional patients who had advanced EA, we evaluated the correlation of miR-196a with its in silico-predicted targets, keratin 5 (KRT5), small proline-rich protein 2C (SPRR2C), and S100 calcium-binding protein A9 (S100A9), which are down-regulated during BE progression. MiR-196a levels inversely correlated with the predicted target mRNA levels in EA. We confirmed that miR-196a specifically targets KRT5, SPRR2C, and S100A9 3' UTRs using miR-196a-mimic and luciferase reporter-based assays. In conclusion, this study identified miR-196a as a potential marker of progression of BE and KRT5, SPRR2C, and S100A9 as its targets.

Empathic Understanding

Empathy is the theoretical and philosophical foundation of self-psychological treatment. By emphasizing empathy as the primary methodology for collecting data about our patients, Kohut subtly, but dramatically, shifted psychoanalysis from Freud's theory-based treatment to a patient-centered treatment in which there is a profound shift in the analyst's listening perspective. This chapter explores the implications of such a shift in our listening perspective for both psychoanalytic treatment and developmental understanding. Using verbatim dialogue from both patient-therapist interactions and parent-child interactions, it delineates empathy's important role in therapeutic healing as well as its growth-promoting functions in a child's development.