Glucocorticoids, tumor necrosis factor-α, and epidermal growth factor regulation of pulmonary morphogenesis: a multivariate in vitro analysis of their related actions

Melnick, Michael; Choy, Henry A.; Jaskoll, Tina

doi:10.1002/(sici)1097-0177(199604)205:4<365::aid-aja1>3.0.co;2-g

Cited by 20 publications

(2 citation statements)

References 43 publications

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“…This results, most likely, from the coexistence of complexity and deterministic chaos (Kolmogorov-Arnold-Moser theorem) within the molecular and energetistic structure of cells [6,7,12]. Consequently, either metabolism [44][45][46], cytoskeletal patterns [47], calcium sequestration [48], tissue morphological patterns in normal or tumor tissues [6,[49][50][51][52][53], or tissue growth [54,55] possess fractal dimension. The fractal dimension reflects the intriguing fact that cells, in spite of the daily experience in the three-dimensional euclidean reality, which approximates geometric reality, are intermediate between two-dimensional surfaces and three-dimensional objects, and possess a fractal structure.…”

Section: Nonlinearity Complexity and Fractal Structurementioning

confidence: 99%

“…Without invalidating molecular findings, complexity offers an alternative, quasi-deterministic interpretation of cellular events underlying phenotype formation and tumorigenesis. The following points need to be emphasized as crucial consequences of the available experimental data: the relationship between genotype and phenotype reflects nonbijective interaction between static and dynamic categories [6,[24][25][26]30,31] leading to nonlinearity of the intra-and intercellular interactions [6,8,9,24], nonlinearity implies the existence of the fractal structure of space of cellular events [6,[44][45][46][47][48][49][50][51][52][53][54][55]. Those features support an holistic rather than a reductionist approach to cellular and cancer biology.…”

Section: Practical Inferencesmentioning

confidence: 99%

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On the holistic approach in cellular and cancer biology: Nonlinearity, complexity, and quasi-determinism of the dynamic cellular network

Waliszewski

Molski²,

Konarski³

1998

J. Surg. Oncol.

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A keystone of the molecular reductionist approach to cellular biology is a specific deductive strategy relating genotype to phenotype—two distinct categories. This relationship is based on the assumption that the intermediary cellular network of actively transcribed genes and their regulatory elements is deterministic (i.e., a link between expression of a gene and a phenotypic trait can always be identified, and evolution of the network in time is predetermined). However, experimental data suggest that the relationship between genotype and phenotype is nonbijective (i.e., a gene can contribute to the emergence of more than just one phenotypic trait or a phenotypic trait can be determined by expression of several genes). This implies nonlinearity (i.e., lack of the proportional relationship between input and the outcome), complexity (i.e. emergence of the hierarchical network of multiple cross‐interacting elements that is sensitive to initial conditions, possesses multiple equilibria, organizes spontaneously into different morphological patterns, and is controled in dispersed rather than centralized manner), and quasi‐determinism (i.e., coexistence of deterministic and nondeterministic events) of the network. Nonlinearity within the space of the cellular molecular events underlies the existence of a fractal structure within a number of metabolic processes, and patterns of tissue growth, which is measured experimentally as a fractal dimension. Because of its complexity, the same phenotype can be associated with a number of alternative sequences of cellular events. Moreover, the primary cause initiating phenotypic evolution of cells such as malignant transformation can be favored probabilistically, but not identified unequivocally. Thermodynamic fluctuations of energy rather than gene mutations, the material traits of the fluctuations alter both the molecular and informational structure of the network. Then, the interplay between deterministic chaos, complexity, self‐organization, and natural selection drives formation of malignant phenotype. This concept offers a novel perspective for investigation of tumorigenesis without invalidating current molecular findings. The essay integrates the ideas of the sciences of complexity in a biological context. J. Surg. Oncol. 1998;68:70–78. © 1998 Wiley‐Liss, Inc.

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Section: Nonlinearity Complexity and Fractal Structurementioning

confidence: 99%

Section: Practical Inferencesmentioning

confidence: 99%

On the holistic approach in cellular and cancer biology: Nonlinearity, complexity, and quasi-determinism of the dynamic cellular network

Waliszewski

Molski²,

Konarski³

1998

J. Surg. Oncol.

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Developmental expression and CORT-regulation of TGF-β and EGF receptor mRNA during mouse palatal morphogenesis: Correlation between CORT-induced cleft palate and TGF-β2 mRNA expression

et al. 1996

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Glucocorticoids (CORT) have been shown to induce cleft palate in mice. Although the pathogenetic pathway of CORT‐induced cleft palate has been investigated for several decades, the molecular details remain to be elucidated. Since growth factors have been shown to regulate palate morphogenesis, and the expression of several growth factors or their receptors, e.g. TGF‐β, EGF receptor (EGF‐R), are known to be modulated by CORT, we postulate that CORT modulation of growth factor (or receptor) gene expression is a key mechanism involved in CORT‐induced cleft palate. To test this hypothesis, we analyzed the steady‐state levels (Northern and RNase protection) and developmental expression (in situ hybridization) of four CORT‐responsive genes—TGF‐β1, TGF‐β2, TGF‐β3, and EGF receptor (EGF‐R)—in developing mouse palates in the presence or absence of exogenous CORT. Pregnant B10.A dams were injected on day 12 of gestation with CORT or sham‐injected and embryonic palates were collected at 1, 2, and 3 days postinjection (E13–E15). During mouse palate development, significant increases in TGF‐β1 and TGF‐β3 mRNA levels, as well as a significant decrease in TGF‐β2 mRNA levels, are detected; no significant difference in EGF‐R transcript level is observed with progressive development. In CORT‐exposed palates, we demonstrate no significant differences in the direction or magnitude of change with time in TGF‐β1, TGF‐β3, and EGF‐R mRNA levels compared to controls. However, CORT delays by 1 day the down‐regulation of palatal TGF‐β2 transcript normally seen on day 14 of gestation. TGF‐β2 is known to inhibit cell proliferation. The level of TGF‐β2 mRNA, the only isoform primarily expressed in the palatal mesenchyme, significantly decreases with progressive palatal development; this down‐regulation in TGF‐β2 expression is associated with increased mesenchymal cell proliferation and palatal shelf growth. CORT, at a critical stage of palatogenesis, induces a delay in the normal down‐regulation of TGF‐β2 gene expression. Given that CORT is known to inhibit mesenchymal cell proliferation and palatal shelf growth, we conclude that the CORT‐induced delay in the normal down‐regulation of TGF‐β2 gene expression is probably a key event in the pathogenesis of CORT‐induced cleft palate. © 1996 Wiley‐Liss, Inc.

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Epidermal growth factor system is a physiological regulator of development of the mouse fetal submandibular gland and regulates expression of the α6-integrin subunit

Kashimata

Gresik

1997

Dev. Dyn.

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Glucocorticoids, tumor necrosis factor-α, and epidermal growth factor regulation of pulmonary morphogenesis: a multivariate in vitro analysis of their related actions

Cited by 20 publications

References 43 publications

On the holistic approach in cellular and cancer biology: Nonlinearity, complexity, and quasi-determinism of the dynamic cellular network

On the holistic approach in cellular and cancer biology: Nonlinearity, complexity, and quasi-determinism of the dynamic cellular network

Developmental expression and CORT-regulation of TGF-β and EGF receptor mRNA during mouse palatal morphogenesis: Correlation between CORT-induced cleft palate and TGF-β2 mRNA expression

Epidermal growth factor system is a physiological regulator of development of the mouse fetal submandibular gland and regulates expression of the α6-integrin subunit

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