Growth‐inhibitory effect of TGF‐B on human fetal adrenal cells in primary monolayer culture

Riopel, Lise; Branchaud, Charlotte L.; Goodyer, Cynthia G.; Adkar, Vinita; Lefèbvre, Yves

doi:10.1002/jcp.1041400207

Cited by 34 publications

(16 citation statements)

References 23 publications

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“…In agreement with our findings, the peptide factor ß-transforming growth factor (ß-TGF) had no mito¬ genic effect in vitro for the fetal zone of the human fetal adrenal gland (Riopel, Branchaud, Goodyer et al 1987). However, there is evidence that the action of ß-TGF on cells is bifunctional: stimulating cell growth in certain instances, and inhibiting cell growth in others, particularly at concentrations less than 1 pg/1 (Roberts, Anzano, Wakefield et al 1985).…”

Section: Discussionsupporting

confidence: 88%

Insulin-like growth factor (IGF)-II and insulin, but not IGF-I, are mitogenic for fetal rat adrenal cells in vitro

Dijk

Tanswell²,

Challis³

1988

Journal of Endocrinology

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The agents controlling growth of the fetal adrenal gland are poorly defined. The purpose of the present study was to determine the factors required to promote proliferation of adrenal cells obtained from fetal rats at 20 days of gestation and grown in monolayer cell culture under serum-free conditions. Insulin stimulated [3H] thymidine incorporation into DNA at all concentrations (0.01-10 mg/l) tested. Rat insulin-like growth factor (IGF)-II in the presence of insulin promoted a dose-dependent increase in mitogenic activity, with a half-maximal concentration of approximately 1 microgram/l; IGF-II had no effect in the absence of insulin. There was no significant effect of IGF-I on mitogenic activity in the presence or absence of insulin. Adrenal cell DNA synthesis was not stimulated by ACTH, several ACTH-related peptides, a variety of known growth factors, several steroids, or conditioned medium from fetal adrenal cells. We conclude that in the presence of insulin, IGF-II is a specific growth factor for the fetal rat adrenal. We also suggest that rat fetal adrenal cells, in common with other epithelial cell types under serum-free culture conditions, may respond to this progression factor without an obligatory requirement for an initial exposure to competence factors.

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Section: Discussionsupporting

confidence: 88%

Insulin-like growth factor (IGF)-II and insulin, but not IGF-I, are mitogenic for fetal rat adrenal cells in vitro

Dijk

Tanswell²,

Challis³

1988

Journal of Endocrinology

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“…It has also been reported that TGF-␤1 was able to inhibit cell proliferation (30); this seems to be achieved by the arrest of the cell cycle progression (31). In fact, we observed inhibition of proliferation (decrease in cell cycle progression speed) in human leukemic MO7e cells by TGF-␤1 (data not shown).…”

Section: Discussionmentioning

confidence: 93%

Cell Density-dependent Apoptosis in HL-60 Cells, Which Is Mediated by an Unknown Soluble Factor, Is Inhibited By Transforming Growth Factor β1 and Overexpression of Bcl-2

Saeki¹,

Yuo²,

Kato³

et al. 1997

Journal of Biological Chemistry

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We report a novel mode of apoptosis induction observed in human leukemic HL-60 cells. These cells spontaneously underwent apoptosis in the course of proliferation when the cell density became higher than 1 ؋ 10 6 /ml. This occurred under ordinary in vitro culture conditions, with or without fetal calf serum. Even the low density cells were committed to undergo apoptosis if they were cultured under artificially concentrated conditions. Replacement of the culture supernatant of the low density cells by that of the high density ones resulted in apoptosis induction in the former cells. This apoptosis-inducing activity of the high density cell culture supernatant was completely eliminated by the action of trypsin but was fully restored following ultrafiltration by 3-kDa pore-sized membrane. A strong apoptosis-inducing activity was recovered from the culture supernatant of the high density HL-60 cells at a specific fraction in reverse-phase column chromatography. Neither an interleukin-␤ converting enzyme inhibitor nor CPP-32 inhibitor blocked the induction of cell density-dependent apoptosis in HL-60 cells, although overexpression of Bcl-2 protein markedly attenuated the induction of this mode. Surprisingly, transforming growth factor-␤1 and activin A did not induce but, rather, inhibited the induction of cell density-dependent apoptosis. These data suggest that HL-60 cells release an unknown low molecular weight peptide-containing factor in response to an increase in cell density to induce apoptosis in an autocrine manner and that the interleukin-␤ converting enzyme-independent intracellular machinery for this mode of apoptosis is strongly affected by signaling events through the transforming growth factor-␤1 receptor and by the action of Bcl-2 oncoprotein.

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“…TGFh regulates adrenal development (22,23) and can inhibit adrenal steroid production (43,44). TGFh can act either as a tumor suppressor or promote cancer progression.…”

Section: Discussionmentioning

confidence: 99%

“…TGFh is also involved in the regulation of human fetal adrenal development. TGFh may exert an antimitotic effect on human fetal adrenal cells in vitro (22,23). Moreover, previous studies suggested an interaction between cAMP/PKA and TGFh pathways (24,25).…”

Section: Introductionmentioning

confidence: 93%

Inactivation of the Carney Complex Gene 1 (Protein Kinase A Regulatory Subunit 1A) Inhibits SMAD3 Expression and TGFβ-Stimulated Apoptosis in Adrenocortical Cells

et al. 2009

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The cyclic AMP signaling pathway can be altered at multiple levels in endocrine tumors. Its central component is the protein kinase A (PKA). Carney complex (CNC) is a hereditary multiple neoplasia syndrome resulting from inactivating mutations of the gene encoding the PKA type I A regulatory subunit (PRKAR1A). Primary pigmented nodular adrenocortical disease is the most frequent endocrine tumor of CNC. Transforming growth factor B (TGFB) regulates adrenal cortex physiology and signals through SMAD2/3. We used an interference approach to test the effects of PRKAR1A inactivation on PKA and TGFB pathways and on apoptosis in adrenocortical cells. PRKAR1A silencing stimulates PKA activity and increases transcriptional activity of a PKA reporter construct and expression of the endogenous PKA target, NR4A2, under basal conditions or after forskolin stimulation. PRKAR1A inactivation also decreased SMAD3 mRNA and protein levels via PKA, altering the cellular response to TGFB. SMAD3 expression was also inhibited by adrenocorticorticotropic hormone in the mouse adrenal gland and by forskolin in H295R cells. TGFB stimulates apoptosis in H295R cells, and this effect was counteracted by PRKAR1A inactivation. PRKAR1A silencing decreased the percentage of apoptotic cells and the cleavage of apoptosis mediators [caspase-3, poly(ADP-ribose) polymerase, and lamin A/C]. Inactivating mutations of PRKAR1A observed in adrenocortical tumors alter SMAD3, leading to resistance to TGFBinduced apoptosis. This cross-talk between the PKA and the TGFB signaling pathways reveals a new mechanism of endocrine tumorigenesis. [Cancer Res 2009;69(18):7278-84]

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Growth‐inhibitory effect of TGF‐B on human fetal adrenal cells in primary monolayer culture

Cited by 34 publications

References 23 publications

Insulin-like growth factor (IGF)-II and insulin, but not IGF-I, are mitogenic for fetal rat adrenal cells in vitro

Insulin-like growth factor (IGF)-II and insulin, but not IGF-I, are mitogenic for fetal rat adrenal cells in vitro

Cell Density-dependent Apoptosis in HL-60 Cells, Which Is Mediated by an Unknown Soluble Factor, Is Inhibited By Transforming Growth Factor β1 and Overexpression of Bcl-2

Inactivation of the Carney Complex Gene 1 (Protein Kinase A Regulatory Subunit 1A) Inhibits SMAD3 Expression and TGFβ-Stimulated Apoptosis in Adrenocortical Cells

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