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PubMed1965

Cell junctions in amphibian skin.

Cell junctions have been investigated in the amphibian epidermis, a stratified squamous epithelium, and compared to those described previously in simple columnar epithelia of mammalian cavitary organs. In adult frogs and toads, and in larvae approaching metamorphosis, belts of membrane fusion or zonulae occludentes of considerable depth are regularly found between adjoining cells of the outermost layer of the stratum corneum, binding the cells together into a continuous, uninterrupted sheet. Another set of occluding zonules appears in the second cornified layer (when such a layer is present), and a third set usually occurs in the outermost layer of the stratum granulosum. Specialized elements described as "modified" and "composite" desmosomes are encountered along the lateral and basal aspects, respectively, of the cornified cells; ordinary desmosomes and maculae occludentes (i.e., spots of membrane fusion) are found in all other strata. The usual 200 A intercellular gap is generally maintained between the cells of the stratum germinativum at the basal ends of the intercellular spaces. Hence, the intercellular spaces of the epidermis form a largely continuous network, closed to the external medium and open to the dermal interstitia. The situation is comparable to that found in columnar epithelia, except that the intercellular spaces are much more extensive, and an extracellular subcompartment (or two) apparently exists in the stratum corneum and between the latter and the stratum granulosum. The last subcompartment is usually filled with a dense substance, probably derived from discharged secretory granules. The tripartite junctional complex characteristic of lumen-lining epithelia (i.e., a zonula occludens followed by a zonula adhaerens, and desmosome) is seen only in early larvae; in adults and in larvae approaching metamorphosis, the occluding zonule is followed directly by a series of modified desmosomes. Interpreted in the light of current physiological data, these findings suggest that the diffusion of water, ions, and small, water-soluble molecules is impeded along the intercellular spaces of the epidermis by zonulae occludentes while it is facilitated from cell to cell within the epidermis by zonulae and maculae occludentes.

Amphibians↗

PubMed2004

Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract.

Given its population of CCR5-expressing, immunologically activated CD4(+) T cells, the gastrointestinal (GI) mucosa is uniquely susceptible to human immunodeficiency virus (HIV)-1 infection. We undertook this study to assess whether a preferential depletion of mucosal CD4(+) T cells would be observed in HIV-1-infected subjects during the primary infection period, to examine the anatomic subcompartment from which these cells are depleted, and to examine whether suppressive highly active antiretroviral therapy could result in complete immune reconstitution in the mucosal compartment. Our results demonstrate that a significant and preferential depletion of mucosal CD4(+) T cells compared with peripheral blood CD4(+) T cells is seen during primary HIV-1 infection. CD4(+) T cell loss predominated in the effector subcompartment of the GI mucosa, in distinction to the inductive compartment, where HIV-1 RNA was present. Cross-sectional analysis of a cohort of primary HIV-1 infection subjects showed that although chronic suppression of HIV-1 permits near-complete immune recovery of the peripheral blood CD4(+) T cell population, a significantly greater CD4(+) T cell loss remains in the GI mucosa, despite up to 5 yr of fully suppressive therapy. Given the importance of the mucosal compartment in HIV-1 pathogenesis, further study to elucidate the significance of the changes observed here is critical.

Acquired Immunodeficiency Syndrome↗

PubMed2000

Syntaxin 17 is abundant in steroidogenic cells and implicated in smooth endoplasmic reticulum membrane dynamics.

The endoplasmic reticulum (ER) consists of subcompartments that have distinct protein constituents, morphological appearances, and functions. To understand the mechanisms that regulate the intricate and dynamic organization of the endoplasmic reticulum, it is important to identify and characterize the molecular machinery involved in the assembly and maintenance of the different subcompartments. Here we report that syntaxin 17 is abundantly expressed in steroidogenic cell types and specifically localizes to smooth membranes of the ER. By immunoprecipitation analyses, syntaxin 17 exists in complexes with a syntaxin regulatory protein, rsly1, and/or two intermediate compartment SNARE proteins, rsec22b and rbet1. Furthermore, we found that syntaxin 17 is anchored to the smooth endoplasmic reticulum through an unusual mechanism, requiring two adjacent hydrophobic domains near its carboxyl terminus. Converging lines of evidence indicate that syntaxin 17 functions in a vesicle-trafficking step to the smooth-surfaced tubular ER membranes that are abundant in steroidogenic cells.

Adrenal Cortex↗

PubMed1997

Heterogeneous distribution of the unusual phospholipid semilysobisphosphatidic acid through the Golgi complex.

To investigate the distribution of lipids through the Golgi complex, we analyzed the envelopes of several viruses that assemble in different subcompartments of the Golgi, as well as subcellular fractions. Our results indicate that each Golgi subcompartment has a distinct phospholipid composition due mainly to differences in the relative amounts of semilysobisphosphatidic acid (SLBPA), sphingomyelin, phosphatidylserine, and phosphatidylinositol. Interestingly, SLBPA is enriched in the adjacent Golgi networks compared with the Golgi stack, and this enrichment varies with cell type. The heterogeneous distribution of SLBPA through the Golgi complex suggests it may play an important role in the structure and/or function of this organelle.

Animals↗

PubMed1999

A model to explain the rapid pressure decrease after air-inflation of diseased middle ears.

OBJECTIVES: Air-inflation in humans and monkeys with significant negative middle ear pressure or with middle ear inflammation was shown to cause greater than ambient middle ear pressure initially, followed by a rapid rate of pressure decrease to approach the preinflation value. STUDY DESIGN: A mathematical model of middle ear pressure regulation is presented and used to simulate air-inflation of the normal and diseased middle ear. MATERIALS AND METHODS: The model represents the total volume of the middle ear as consisting of three subcompartments representing the airspace, effusion, and mucosa/blood. Gas exchange among those compartments was assumed to be diffusion limited, and the gas exchange between the mucosa/blood compartment and systemic blood was assumed to be perfusion limited. Disease was modeled as an increase in mucosal blood flow or, alternatively, as an increase in the volumes of the effusion and mucosa/blood compartments. RESULTS: The predictions of the model agree better with the experimental data when the increased rate of pressure change after middle ear inflation in diseased ears is driven by an increased volume of the effusion compartment as opposed to an increased perfusion rate. The responsible mechanism is a rapid redistribution among subcompartments of the gas volume introduced into the air compartment. CONCLUSIONS: These results suggest that middle ear inflation with inert gas can be used to diagnose the presence and relative amount of middle ear effusion, and that current protocols for treating otitis media with effusion using inflation need to be modified to optimize their intended effect.

Animals↗

PubMed1995

Nuclear localization of the human cytomegalovirus tegument protein pp150 (ppUL32).

The human cytomegalovirus (HCMV) basic phosphoprotein pp150, encoded by the UL32 gene, together with the two other major phosphoproteins, pp65 (ppUL83) and pp71 (ppUL82) and several minor structural proteins, form the tegument around the viral nucleocapsid. Experiments were undertaken to locate the area of assembly of tegument proteins pp150 and pp65 and nucleocapsids in fibroblasts, in order to assess the functional role of these two structural proteins in HCMV morphogenesis. Whereas pp150 expression starts during the cytoplasmic maturation of HCMV, pp65 is expressed in the early and late phases of HCMV gene transcription. Western blot analysis of isolated cell fractions showed that pp150 is initially (48 h post-infection) localized in the nucleus, associated either with the nuclear membrane or with viral assembly regions, and later (72 h post-infection) in the cytoplasm. By indirect immunofluorescence, pp150 and pp65 could be detected in nuclear subcompartments and were strongly associated with the nuclear membrane. Using immunogold analysis by electron microscopy, pp65 was exclusively detected within the matrix of cytoplasmic and extracellular dense bodies and of dense body-like structures in the nucleoplasm. These were localized in close contact with hypertrophic nucleoli, in the proximity of developing nucleocapsids and in special patches at the inner nuclear membrane. Positive immunostaining of pp150 was observed at the surface of developing nucleocapsids concentrated within viral assembly regions in the nucleoplasm. Additionally, the tegument of cytoplasmic and extracellular virions was stained, whereas dense bodies or nuclear dense body-like structures did not react. Thus, the acquisition of the tegument protein pp150 seems to start in special nuclear subcompartments of the HCMV-infected fibroblasts.

Cell Fractionation↗

PubMed1997

Localization of Xenopus Vg1 mRNA by Vera protein and the endoplasmic reticulum.

In many organisms, pattern formation in the embryo develops from the polarized distributions of messenger RNAs (mRNAs) in the egg. In Xenopus, the mRNA encoding Vg1, a growth factor involved in mesoderm induction, is localized to the vegetal cortex of oocytes. A protein named Vera was shown to be involved in Vg1 mRNA localization. Vera cofractionates with endoplasmic reticulum (ER) membranes, and endogenous Vg1 mRNA is associated with a subcompartment of the ER. Vera may promote mRNA localization in Xenopus oocytes by mediating an interaction between the Vg1 3' untranslated region and the ER subcompartment.

Animals↗

PubMed1977

Volume changes in sarcoplasmic reticulum of rat hearts perfused with hypertonic solutions.

To explore whether morphometry of intracellular membrane-limited subcompartments can be used to follow physiological volume changes in such subcompartments in hearts rapidly fixed by perfusion fixation, we have measured osmotically induced volume changes in electron micrographs of longitudinally oriented sarcoplasmic reticulum (LSR) and terminal cisterns (TC) of rat left ventricular myocardial cells. Vascular perfusion with solutions whose osmolality varied from 0.67 to 1.88 isomolal showed that in the hyperosmolal range LSR volume decreased linearly. Approximately 79% of LSR luminal volume participated in the osmotic rey unresponsive. By contrast, we found that the TC responded by dilation when hearts were perfused with hypersomolal NaCl, NaI, LiCl, or sucrose. Furthermore, with hyperosmolal NaCl the dilation developed within 1 minute; its rate and extent of development were concentration-dependent; it manifested an obligate association with prior or concomitant T-tubular dilation and was not readily reversible. We conclude that (1) the technique sensitively measures in situ changes of LSR volume; (2) most of LSR luminal water is osmotically responsive, but a significant fraction may not be; (3) exposure to hyperosomolal solutions may bring about (perhaps irreversible) structural changes in the diadic membrane complex, leading to changes in its solute permeability.

Animals↗

PubMed2003

Gene expression analysis in response to lung toxicants: I. Sequencing and microarray development.

A key challenge in measuring gene expression changes in the lung in response to site-selective toxicants is differentiating between target and nontarget areas. The toxicity for the cytotoxicant 1-nitronaphthalene is highly localized in the airway epithelium. Target cells comprise but a fraction of the total lung cell mass; measurements from whole lung homogenates are not likely to reflect what occurs at the target site. Additionally, the use of generic microarrays to measure expression in airway epithelium may not provide a good representation of transcripts present at the site of toxic action. cDNA libraries from airway and alveolar subcompartments of rat lung were sequenced for the development of a custom microarray representative of these lung regions. We identified 7,460 nonredundant rat lung sequences. Nearly 30% of the sequences on this array are not present on the Affymetrix Rat GeneChip 230. A 20,000-element microarray was developed that delineates differences in gene expression between subcompartments. This is the first in a series of articles employing this microarray for detecting gene expression changes during acute injury produced by 1-nitronaphthalene and subsequent repair.

Animals↗

PubMed1985

Development of an integrated model for analysis of the kinetics of apolipoprotein B in plasma very low density lipoproteins, intermediate density lipoproteins, and low density lipoproteins.

To quantify more precisely the metabolism of apolipoprotein B (apo B) in human beings, an integrated model was developed for the analysis of the isotope kinetics of apo B in very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and low density lipoproteins (LDL). The experimental basis for model development was a series of 30 triple-isotope studies in which patients received autologous 131I-VLDL, 125I-IDL, and [3H]glycerol as a precursor of VLDL triglycerides. The currently proposed model contains the following components: (a) a VLDL delipidation cascade that has a variable number of subcompartments, (b) a slowly catabolized pool of VLDL, (c) an IDL compartment consisting of two closely connected subcompartments, one of which is outside the immediate circulation, and (d) a two-compartment subsystem for LDL. Because mass data indicate that not all VLDL were converted to LDL, the model allows for irreversible removal of apo B from VLDL (or IDL) subsystems. It accounts for apparent "direct" input of LDL by postulating an early, rapidly metabolized compartment of VLDL that is converted directly to IDL. The model appears to be consistent with specific activity curves from the current triple-isotope studies and with present concepts of lipoprotein physiology; it also can be used to quantify pathways of lipoprotein apo B transport in normal and abnormal states.

Apolipoproteins B↗

PubMed2005

Nuclear substructure reorganization during late-stage erythropoiesis is selective and does not involve caspase cleavage of major nuclear substructural proteins.

Enucleation, a rare feature of mammalian differentiation, occurs in 3 cell types: erythroblasts, lens epithelium, and keratinocytes. Previous investigations suggest that caspase activation functions in lens epithelial and keratinocyte enucleation, as well as in early erythropoiesis encompassing erythroid burst-forming unit (BFU-E) differentiation to proerythroblast. To determine whether caspase activation contributes to later erythropoiesis and whether nuclear substructures other than chromatin reorganize, we analyzed distributions of nuclear subcompartment proteins and assayed for caspase-induced cleavage of subcompartmental target proteins in mouse erythroblasts. We found that patterns of lamin B in the filamentous network interacting with both the nuclear envelope and DNA, nuclear matrix protein NuMA (Nuclear mitotic apparatus), and splicing factors Sm and SC35 persisted during nuclear condensation, consistent with effective transcription of genes expressed late in differentiation. Thus, nuclear reorganization prior to enucleation is selective, allowing maintenance of critical transcriptional processes independent of extensive chromosomal reorganization. Consistent with these data, we found no evidence for caspase-induced cleavage of major nuclear subcompartment proteins during late erythropoiesis, in contrast to what has been observed in early erythropoiesis and in lens epithelial and keratinocyte differentiation. These findings imply that nuclear condensation and extrusion during terminal erythroid differentiation involve novel mechanisms that do not entail major activation of apoptotic machinery.

Animals↗

PubMed2006

Role of cellular compartmentation in the metabolic response to stress: mechanistic insights from computational models.

The mechanisms controlling ATP generation in the transition from normal resting conditions to either high work states or ischemia are poorly understood. ATP generation depends upon compartmentation between the mitochondria and cytosol of metabolic pathways and key energy transfer species that cannot be easily assessed experimentally. We developed a multicompartment mathematical model of cardiac metabolism to simulate the metabolic responses to ischemia and increased workload. The model is based on mass balances, transport, and metabolic processes in cardiac tissue, and has three distinct compartments (blood, cytosol, and mitochondria). In addition to distinguishing between cytosol and mitochondria, the model includes a cytosolic subcompartment for glycolytic metabolic channeling. The model simulations predict the rapid activation of glycogenolysis and lactate production at the onset of ischemia, and support the concept of localization of glycolysis to a cytosolic subcompartment. In addition, simulations show that mitochondrial NADH/NAD(+) is primarily determined by oxygen consumption during ischemia, while cytosolic NADH/NAD(+) and lactate production are largely a function of glycolytic flux during the initial phase, and is controlled by mitochondrial NADH/NAD(+) and the malate-aspartate shuttle during the steady state. Finally, the model predicts that metabolic activation with an abrupt increase in workload requires parallel activation of ATP hydrolysis, glycolysis, mitochondrial dehydrogenases, the electron transport chain, and ADP phosphorylation. Taken together, these studies demonstrate the importance of metabolic compartmentation in the regulation of cardiac energetics in response to acute stress, and they highlight the usefulness of computational models in this line of investigation.

Animals↗

PubMed2005

A unique lysophospholipid acyltransferase (LPAT) antagonist, CI-976, affects secretory and endocytic membrane trafficking pathways.

Previous studies have shown that inhibition of a Golgi-complex-associated lysophospholipid acyltransferase (LPAT) activity by the drug CI-976 stimulates Golgi tubule formation and subsequent redistribution of resident Golgi proteins to the endoplasmic reticulum (ER). Here, we show that CI-976 stimulates tubule formation from all subcompartments of the Golgi complex, and often these tubules formed independently, i.e. individual tubules usually did not contain markers from different subcompartments. Whereas the cis, medial and trans Golgi membranes redistributed to the ER, the trans Golgi network (TGN) collapsed back to a compact juxtanuclear position similar to that seen with brefeldin A (BFA) treatment. Also similar to BFA, CI-976 induced the formation of endosome tubules, but unlike BFA, these tubules did not fuse with TGN tubules. Finally, CI-976 produced an apparently irreversible block in the endocytic recycling pathway of transferrin (Tf) and Tf receptors (TfRs) but had no direct effect on Tf uptake from the cell surface. Tf and TfRs accumulated in centrally located, Rab11-positive vesicles indicating that CI-976 inhibits export of cargo from the central endocytic recycling compartment. These results, together with previous studies, demonstrate that CI-976 inhibits multiple membrane trafficking steps, including ones found in the endocytic and secretory pathways, and imply a wider role for lysophospholipid acyltransferases in membrane trafficking.

1-Acylglycerophosphocholine O-Acyltransferase↗

PubMed2006

The transcriptional regulator CBP has defined spatial associations within interphase nuclei.

It is becoming increasingly clear that nuclear macromolecules and macromolecular complexes are compartmentalized through binding interactions into an apparent three-dimensionally ordered structure. This ordering, however, does not appear to be deterministic to the extent that chromatin and nonchromatin structures maintain a strict 3-D arrangement. Rather, spatial ordering within the cell nucleus appears to conform to stochastic rather than deterministic spatial relationships. The stochastic nature of organization becomes particularly problematic when any attempt is made to describe the spatial relationship between proteins involved in the regulation of the genome. The CREB-binding protein (CBP) is one such transcriptional regulator that, when visualised by confocal microscopy, reveals a highly punctate staining pattern comprising several hundred individual foci distributed within the nuclear volume. Markers for euchromatic sequences have similar patterns. Surprisingly, in most cases, the predicted one-to-one relationship between transcription factor and chromatin sequence is not observed. Consequently, to understand whether spatial relationships that are not coincident are nonrandom and potentially biologically important, it is necessary to develop statistical approaches. In this study, we report on the development of such an approach and apply it to understanding the role of CBP in mediating chromatin modification and transcriptional regulation. We have used nearest-neighbor distance measurements and probability analyses to study the spatial relationship between CBP and other nuclear subcompartments enriched in transcription factors, chromatin, and splicing factors. Our results demonstrate that CBP has an order of spatial association with other nuclear subcompartments. We observe closer associations between CBP and RNA polymerase II-enriched foci and SC35 speckles than nascent RNA or specific acetylated histones. Furthermore, we find that CBP has a significantly higher probability of being close to its known in vivo substrate histone H4 lysine 5 compared with the closely related H4 lysine 12. This study demonstrates that complex relationships not described by colocalization exist in the interphase nucleus and can be characterized and quantified. The subnuclear distribution of CBP is difficult to reconcile with a model where chromatin organization is the sole determinant of the nuclear organization of proteins that regulate transcription but is consistent with a close link between spatial associations and nuclear functions.

Acetylation↗

PubMed1985

Electron microscopic analysis of lymphocyte nuclei in non-Hodgkin's lymphoma.

Ultrastructural studies of normal and neoplastic lymphocytes are presented that qualitatively and quantitatively assess the central cell organelle currently used by surgical pathologists in the classification of non-Hodgkin's lymphoma, the nucleus. Events occurring during normal lymphocyte transformation can be used to appreciate essential mechanisms involved in producing the appearance of the nucleus as seen by microscopy. Quantitation of nuclear subcompartments by morphometric image analysis reveals that determination of nuclear size is primarily due to the ribonucleoprotein materials distributed between condensed chromatin masses, the interchromatinic (euchromatin or nuclear matrix) region. Furthermore, such investigations show that amounts and distribution of condensed chromatin in lymphocyte nuclei cannot be adequately assessed from routine histologic sections. Ultrastructural morphometric analysis of representative cases of the principal subtypes of NHL indicates that the atypical morphologic appearance of neoplastic lymphocytes results from a complex interplay between total amounts of condensed chromatin in nuclei and the size of individual aggregates of condensed chromatin, one or both of which may be abnormal in NHL. Abnormalities of interchromatinic materials are also likely involved in ordering the gross appearance of the nucleus. Understanding of both the dynamic capabilities of the nucleus, and the organization of and interplay between the various subcompartments of this organelle will be helpful in improving the classification of NHL by surgical pathologists.

Animals↗

PubMed1991

De Quervain's syndrome: surgical and anatomical studies of the fibroosseous canal.

Anatomical variations of the first dorsal fibroosseous compartment were studied in 70 patients (38 women, 32 men) who underwent surgical release of the tendons. Seventy-one dissected forearms were also studied. De Quervain's tenosynovitis was the only diagnosis for two thirds of the patients. Nonoperative treatment for all of these patients failed. Forty-three patients (61%) had job-related symptoms. Recovery ranged from 3 to 36 months postoperatively (mean: 4.5 months). Multiple subcompartments were recorded in 47% of patients and in 75% of anatomic specimens. In 94% of the specimens, the abductor pollicis longus (APL) tendon had two to four slips, but in only two were there multiple extensor pollicis brevis (EPB) tendons. Surgeons must recognize that multiple APL tendon slips and two subcompartments are the rule, rather than the exception, in normal anatomy.

Adolescent↗

PubMedDate not supplied

Integrative properties of the Pe1 neuron, a unique mushroom body output neuron.

A mushroom body extrinsic neuron, the Pe1 neuron, connects the peduncle of the mushroom body (MB) with two areas of the protocerebrum in the honeybee brain, the lateral protocerebral lobe (LPL) and the ring neuropil around the alpha-lobe. Each side of the bee brain contains only one Pe1 neuron. Using a combination of intracellular recording and neuroanatomical techniques we analyzed its properties of integrative processing of the different sensory modalities. The Pe1 neuron responds to visual, mechanosensory, and olfactory stimuli. The responses are broadly tuned, consisting of a sustained increase of spike frequency to the onset and offset of light flashes, to horizontal and vertical movements of extended objects, to mechanical stimuli applied to the antennae or mouth parts, and to all olfactory stimuli tested (29 chemicals). These multisensory properties are reflected in its dendritic organization. Serial reconstructions of intracellularly stained Pe1 neurons using confocal microscopy reveal that the Pe1 neuron arborizes throughout all layers of MB peduncle with finger-like, vertically oriented dendrites. The peduncle of the MB is formed by the axons of Kenyon cells, whose dendritic inputs are organized in modality-specific subcompartments of the calyx region. The peduncular arborization indicates that the Pe1 neuron receives input from Kenyon cells of all calycal subcompartments. Because the Pe1 neuron changes its odor responses transiently as a consequence of olfactory learning, we hypothesize that the multimodal response properties might have a role in memory consolidation and help to establish contextual references in the long-term trace.

Adaptation, Physiological↗

PubMed2003

The role of transforming growth factor alpha in determining growth factor independence.

Growth factor independence is a hallmark of malignancy that is attributed to the development of autocrine growth factor loops in cancer cells. However, growth factor-dependent normal cells also exhibit autocrine activity, thus raising the issue of how endogenously produced activity in cancer cells differs in a manner that leads to growth factor independence. We have examined this issue by comparing growth factor-independent HCT116 human colon carcinoma cells with a growth factor-dependent subcompartment of malignant cells designated HCT116b that was isolated from the same patient tumor. Therefore, the development of the growth factor-independent phenotype represents clonal progression within the tumor in vivo. The growth factor independence of HCT116 cells was shown to be dependent on autocrine transforming growth factor (TGF)-alpha activity, yet the isoparental HCT116b subcompartment showed similar levels of TGF-alpha expression as HCT116 when cells were in exponential growth. When both cell lines were growth arrested by nutrient deprivation, HCT116b cells required nutrient replenishment and growth factors for reinitiation of DNA synthesis, whereas HCT116 cells required only nutrient replenishment. In contrast to growth factor-dependent HCT116b cells, the HCT116 cells showed up-regulation of TGF-alpha expression during growth arrest as a result of enhanced transcription. This increased TGF-alpha expression in quiescent HCT116 cells was associated with constitutive epidermal growth factor receptor (EGFR) activation in the growth-arrested state, whereas growth-arrested HCT116b cells did not show EGFR activation. TGF-alpha antisense transfection of HCT116 cells showed that EGFR activation was due to increased TGF-alpha expression. Pretreatment of growth-arrested HCT116 cells with AG1478, a selective inhibitor of EGFR tyrosine kinase activity, blocked the reinitiation of DNA synthesis, demonstrating that growth factor independence was due to the increased TGF-alpha expression and EGFR activation of these cells in growth arrest relative to growth factor-dependent HCT116b cells. Importantly, the level of EGFR activation in growth-arrested HCT116 cells was only slightly higher than that of exponential cells, indicating that it was inappropriate EGFR activation in growth arrest rather than the amplitude of activation that generated growth factor independence.

Animals↗