Thyroid Hormone Induction of an Autocrine Growth Factor Secreted by Pituitary Tumor Cells

Hinkle, PM; Kinsella, PA

doi:10.1126/science.3097825

Cited by 56 publications

(29 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast to cells making paracrine-only growth factor, producers of autocrine growth factor usually spread to fixation. It is interesting that autocrine growth factor production is observed in many tumours (Sporn and Roberts, 1985;Hinkle and Kinsella, 1986;Knabbe et al, 1987;Ensoli et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

Modelling the consequences of interactions between tumour cells

Tomlinson¹,

Bodmer²

1997

Br J Cancer

View full text Add to dashboard Cite

Summary Classical models of tumorigenesis assume that the mutations which cause tumours to grow act in a cell-autonomous fashion. This is not necessarily true. Sometimes tumour cells may adopt genetic strategies that boost their own replication and which also influence other cells in the tumour, whether directly or as a side-effect. Tumour growth as a whole might be enhanced or retarded. We have used mathematical models to study two non-autonomous strategies that tumour cells may use. First, we have considered the production by tumour cells of an angiogenesis growth factor that benefits both the cell from which it originates and neighbouring cells. Second, we have analysed a situation in which tumour cells produce autocrine-only or paracrine-only growth factors to prevent programmed cell death. In the angiogenesis model, stable genetic polymorphisms are likely to occur between cells producing and not producing the growth factor. In the programmed cell death model, cells with autocrine growth factor production can spread throughout the tumour. Production of paracrine-only growth factor is never selected because it is 'altruistic' (that is of no benefit to the cell that makes the growth factor), despite being potentially beneficial to tumour growth as a whole. No polymorphisms can occur in the programmed cell death model. Production of angiogenesis and other growth factors in tumours may be under stable genetic, rather than epigenetic, control, with implications for therapies aimed at such targets. Many of the mutations observed in tumours may have non-autonomous effects.Keywords: tumorigenesis; cellular interactions; non-autonomous behaviour; polymorphism In classical models of tumorigenesis, mutations that promote tumour growth are usually assumed to have cell-autonomous modes of action Doll, 1954, 1957; Cairns, 1975;Fisher, 1958;Loeb, 1991; Tomlinson and Bodmer, 1995). This assumption may hold for many mutations, but it may not always be valid. We suggest that some mutations might cause tumour cells to adopt strategies that involve interacting with other cells in the tumour. These interactions may take the form of a cell directly influencing another cell, or they may be side-effects of apparently cell-autonomous action. We have constructed specific but simple mathematical models to study the outcome when tumour cells interact with one another.The models below consider a small number of biologically plausible situations and possible behaviours that tumour cells can adopt in these situations. An individual cell's genotype leads inevitably to the adoption of a particular strategy. Given genotype frequencies and selective parameters, it is possible to determine the benefits accruing to each behaviour and the frequencies with which different genotypes interact. Changes in genotype frequency can thus be calculated. At equilibrium, some genotypes will be lost and others fixed in the population, or there will be an internal point of equilibrium (polymorphism).All the models make a number of assumptions. Correspondence...

show abstract

Section: Discussionmentioning

confidence: 99%

Modelling the consequences of interactions between tumour cells

Tomlinson¹,

Bodmer²

1997

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…GH, epidermal growth factor, nerve growth factor) and induce cell growth in various tissues (Ezzat & Melmed 1990, Ray & Melmed 1997. More specifically, with pituitary tumor cells it has been clearly demonstrated that T 3 can induce the production and secretion of a specific pituitary growth factor with selective growth-promoting properties (Hinkle & Kinsella 1986, Ezzat & Melmed 1990.…”

Section: Discussionmentioning

confidence: 99%

Expression and regulation of osteopontin and connective tissue growth factor transcripts in rat anterior pituitary

Ehrchen¹,

Heuer²,

Sigmund³

et al. 2001

Journal of Endocrinology

View full text Add to dashboard Cite

Cell-cell interactions are important regulatory elements in anterior pituitary (AP) physiology. As model systems to study pituitary cell-cell interactions, AP cells kept either as monolayers or as organotypic reaggregate cultures were analyzed by differential display PCR. We identified six cDNA fragments (osteopontin (Opn), connective tissue growth factor (CTGF), v -integrin, cathepsin H, lysozyme and O-acetyl GD 3 ganglioside synthase) that showed elevated expression in monolayers compared with reaggregate cultures and the AP. The adenohypophyseal mRNA expression of Opn and CTGF, two secreted signaling substances, was studied in more detail.In situ hybridization histochemistry revealed that Opn mRNA expression is restricted to a subpopulation of gonadotropes whereas CTGF hybridization signals could not be ascribed to any known cell type. Opn transcript levels were downregulated in the APs of lactating rats and decreased when rats received s.c. injections of 17 -estradiol for 5 days. The mRNA expression was higher in male than in female rats and increased after gonadectomy. CTGF transcript levels were higher in male compared with female rats and were increased in pregnant rats and in rats treated for 5 days with triiodothyronine or dexamethasone.These results indicate that Opn and CTGF may be of physiological importance as local communication factors in the AP.

show abstract

“…However, these findings do not exclude possible non-genomic actions of T 3 on signal transduction pathways. Evidence for a close functional relationship between TH and EGF in the regulation of cellular growth has been obtained in various cellular types (Hinkle & Kinsella 1986, Walker 1986, Kaji & Hinkle 1987, Matsuo et al 1993. Most of the cellular proliferative responses to growth factors are mediated by TK activity (Sibley et al 1988, Dumont et al 1992.…”

Section: Discussionmentioning

confidence: 99%

Tri-iodothyronine induces proliferation in cultured bovine thyroid cells: evidence for the involvement of epidermal growth factor-associated tyrosine kinase activity

Fulvio

Coleoni²,

Pellizas³

et al. 2000

Journal of Endocrinology

View full text Add to dashboard Cite

The effects of the tri-iodothyronine (T 3 ) secreted by thyroid cells on the growth of the thyrocyte are poorly known. In this study we analyzed the effects of T 3 on the proliferation of bovine thyroid follicles in primary culture previously depleted of endogenous T 3 . Cellular deoxiribonucleic acid (DNA) synthesis, determined by [ 3 H]thymidine incorporation, was stimulated by T 3 (0·1-5·0 nM) for 24 h in a concentration-dependent fashion with a maximal effect at 1·0 nM T 3 (P<0·01). This T 3 action was time-dependent when assayed from 12 to 72 h. The induction of mitogenic activity was corroborated by the increase in proliferating cell nuclear antigen (PCNA) measured by Western blot analysis. PCNA increased after treatment with T 3 (0·1-5·0 nM) in a concentrationdependent manner. Since T 3 modifies the activity of growth factors whose actions are mainly mediated by tyrosine kinase (TK) activation in diverse cellular types, we assayed the effects of genistein, a general TK inhibitor, and tyrphostin A25, a specific epidermal growth factor (EGF)-receptor (EGFR)-dependent TK activity inhibitor, on the proliferative effects of T 3 . The T 3 -induced [ 3 H]thymidine incorporation was inhibited by both agents in a concentration-dependent manner. A significant increase in the total TK activity measured in cellular protein extracts was induced by 0·5 and 1·0 nM T 3 (P<0·001). Tyrosine phosphorylation of the EGFR was also stimulated by T 3 (P<0·001) with no change in the EGFR expression as determined by Western blot analysis. Both, the T 3 -stimulated [3 H]thymidine incorporation and the TK activity were inhibited by a anti-mouse EGF antibody. These results lead us to propose that T 3 could operate as a proliferative agent in bovine thyroid cells through a mechanism involving an autocrine/paracrine EGF/EGFR-dependent regulation.

show abstract

Thyroid Hormone Induction of an Autocrine Growth Factor Secreted by Pituitary Tumor Cells

Cited by 56 publications

References 17 publications

Modelling the consequences of interactions between tumour cells

Modelling the consequences of interactions between tumour cells

Expression and regulation of osteopontin and connective tissue growth factor transcripts in rat anterior pituitary

Tri-iodothyronine induces proliferation in cultured bovine thyroid cells: evidence for the involvement of epidermal growth factor-associated tyrosine kinase activity

Contact Info

Product

Resources

About