Modulation of C-myc by transforming growth factor-β in human colon carcinoma cells

Mulder, Kathleen M.; Levine, Alan E.; Hernandez, Xochil; McKnight, Mary K.; Brattain, Diane E.; Brattain, Michael G.

doi:10.1016/0006-291x(88)90449-4

“…Therefore, it is feasible that glucose in SM nutrient replenishment medium stimulates TGFa expression in quiescent FET cells, and that insulin in the TI medium further amplifies this stimulation by increasing the expression of the GFAT enzyme and/or allosteric activation of the enzyme. The second mechanism controlling TGFa transcription involves EGFr activation (Coffey et al, 1992;Mulder, 1991;Zipfel et al, 1993). Raja et al (1991) identified an EGF/ TGFa response element which resides between 0373 -0201 bp of TGFa promoter.…”

Section: Repression Of Autocrine Tgfa Was Controlled 1982) At the Trmentioning

confidence: 98%

“…In contrast, highly aggressive, growth factor-independent HCT116 human colon carcinoma cells aberrantly upregulated this autocrine activity in the quiescent state (Mulder, 1991, Cancer Res., 51:2256-2262 Howell et al, 1998, Mol. Cell.…”

mentioning

confidence: 97%

“…

Previously, we reported that unaggressive, growth factor-dependent FET human colon carcinoma cells downregulated their transforming growth factor alpha (TGFa) expression in a quiescent state (G 0 /G 1 ) induced by growth factor and nutrient deprivation (Mulder, 1991, Cancer Res., 51:2256-2262. In contrast, highly aggressive, growth factor-independent HCT116 human colon carcinoma cells aberrantly upregulated this autocrine activity in the quiescent state (Mulder, 1991, Cancer Res., 51:2256-2262 Howell et al, 1998, Mol.

…”

mentioning

confidence: 99%

“…The protocol was carried out as previously described, with some minor modifications (Mulder and Brattain, sion, perhaps contributing to their malignant progression (Mulder, 1991). In this report, we utilized FET 1989).…”

mentioning

confidence: 99%

“…The colonies were then stained with growth factor-dependent FET human colon carcinoma cells downregulated their TGFa expression at a quies-MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) (Sigma) and photographed. cent state (G 0 /G 1 ) induced by growth factor and nutrient deprivation (Mulder, 1991), but that highly aggres-3 H-thymidine incorporation assay sive, growth factor-independent HCT116 human colon carcinoma cells aberrantly upregulated TGFa expres-…”

mentioning

confidence: 99%

See 3 more Smart Citations

Autocrine TGF? expression in the regulation of initiation of human colon carcinoma growth

Wang

¹

,

Li

²

,

Jiang

³

et al. 1998

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Previously, we reported that unaggressive, growth factor-dependent FET human colon carcinoma cells downregulated their transforming growth factor alpha (TGFalpha) expression in a quiescent state (G0/G1) induced by growth factor and nutrient deprivation (Mulder, 1991, Cancer Res., 51:2256-2262). In contrast, highly aggressive, growth factor-independent HCT116 human colon carcinoma cells aberrantly upregulated this autocrine activity in the quiescent state (Mulder, 1991, Cancer Res., 51:2256-2262; Howell et al., 1998, Mol. Cell. Biol., 18:303-313). In this report, the role of autocrine TGFalpha and the mechanism of its regulation of expression during reentry into the cell cycle from a noncycling growth state were determined in FET cells. Optimal induction of DNA synthesis from a quiescent state in FET cells is dependent upon autocrine TGFalpha as well as exogenous transferrin and insulin. Reentry into the cell cycle resulting from treatment with exogenous transferrin and insulin resulted in approximately 3-fold induction of TGFalpha expression within 1 hr. TGFalpha induction was controlled at the transcription level, and the cis-controlling element was localized to the region between bp -370 - -201 relative to the translation start codon within the TGFalpha promoter. Thus neutralization of autocrine TGFalpha protein revealed that the induced TGFalpha autocrine activity was necessary for DNA synthesis and acted only in the early G1 phase of the cell cycle. Blockade of autocrine TGFalpha expression early in the cell cycle resulted in the reduction of DNA synthesis, whereas treatment with neutralization antibody at later times had no effect. This suggested that autocrine TGFalpha functions to initiate cell growth from noncycling states. This was further confirmed by the dependence of FET cells upon autocrine TGFalpha for colony formation in experiments where the plating density was sufficiently low to generate a lag phase in tissue culture. In contrast, TGFalpha autocrine activity was not required for exponential phase cells, as evidenced by the failure of TGFalpha neutralizing antibody to inhibit proliferation in this growth state. Taken together, these results suggest that autocrine TGFalpha acts primarily in the process of growth initiation by moving cells from a noncycling state back into the cell cycle, rather than supporting cell growth already initiated.

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Differential control of expression of type I and type II receptors of transforming growth factor‐β in colon carcinoma cells

Periyasamy

¹

,

Sun

²

,

Gentry

³

et al. 1996

Journal Cellular Physiology

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We investigated TGF-beta response and the expression of TGF-beta receptors in clones of MOSER colon carcinoma cells (designated MOSER II and MOSER III-10) as a function of their growth state. TGF-beta 1 response as assessed by induction of fibronectin expression was higher (3.0-fold) in exponentially growing cells than in quiescent cells. The expression of type I receptor (RI) mRNA was greater (2.5 to 3.0-fold) in exponentially growing cells than in quiescent cells. In contrast, the expression of type II receptor (RII) mRNA was marginally increased in quiescent cells relative to exponential cells. Nuclear run-off assays, and actinomycin-D treatment indicated that the increased expression of RI mRNA in exponentially growing cells was primarily due to an increase in transcription, while a marginal increase in mRNA level for RII in quiescent cells was primarily due to an increase in mRNA stability. Affinity cross-linking with 125I-labeled TGF-beta 1, showed that the exponentially growing cells displayed greater amounts of 125I TGF-beta 1 binding to RI and RII than quiescent cells, indicating that increased cell surface expression of receptors was correlated with increased response in the exponential growth state. Immunoblot analysis also indicated greater amounts of RI protein in exponential compared to quiescent cells; however, no difference in RII protein was observed in the two growth states. These data indicate that expression of the receptors responsible for TGF-beta signal transduction are differentially controlled.

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Autocrine TGFα expression in the regulation of initiation of human colon carcinoma growth

Wang¹,

Li²,

Wen³

et al. 1998

Self Cite

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Previously, we reported that unaggressive, growth factor-dependent FET human colon carcinoma cells downregulated their transforming growth factor alpha (TGFalpha) expression in a quiescent state (G0/G1) induced by growth factor and nutrient deprivation (Mulder, 1991, Cancer Res., 51:2256-2262). In contrast, highly aggressive, growth factor-independent HCT116 human colon carcinoma cells aberrantly upregulated this autocrine activity in the quiescent state (Mulder, 1991, Cancer Res., 51:2256-2262; Howell et al., 1998, Mol. Cell. Biol., 18:303-313). In this report, the role of autocrine TGFalpha and the mechanism of its regulation of expression during reentry into the cell cycle from a noncycling growth state were determined in FET cells. Optimal induction of DNA synthesis from a quiescent state in FET cells is dependent upon autocrine TGFalpha as well as exogenous transferrin and insulin. Reentry into the cell cycle resulting from treatment with exogenous transferrin and insulin resulted in approximately 3-fold induction of TGFalpha expression within 1 hr. TGFalpha induction was controlled at the transcription level, and the cis-controlling element was localized to the region between bp -370 - -201 relative to the translation start codon within the TGFalpha promoter. Thus neutralization of autocrine TGFalpha protein revealed that the induced TGFalpha autocrine activity was necessary for DNA synthesis and acted only in the early G1 phase of the cell cycle. Blockade of autocrine TGFalpha expression early in the cell cycle resulted in the reduction of DNA synthesis, whereas treatment with neutralization antibody at later times had no effect. This suggested that autocrine TGFalpha functions to initiate cell growth from noncycling states. This was further confirmed by the dependence of FET cells upon autocrine TGFalpha for colony formation in experiments where the plating density was sufficiently low to generate a lag phase in tissue culture. In contrast, TGFalpha autocrine activity was not required for exponential phase cells, as evidenced by the failure of TGFalpha neutralizing antibody to inhibit proliferation in this growth state. Taken together, these results suggest that autocrine TGFalpha acts primarily in the process of growth initiation by moving cells from a noncycling state back into the cell cycle, rather than supporting cell growth already initiated.

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Modulation of C-myc by transforming growth factor-β in human colon carcinoma cells

Cited by 56 publications

References 11 publications

Autocrine TGF? expression in the regulation of initiation of human colon carcinoma growth

Autocrine TGF? expression in the regulation of initiation of human colon carcinoma growth

Differential control of expression of type I and type II receptors of transforming growth factor‐β in colon carcinoma cells

Autocrine TGFα expression in the regulation of initiation of human colon carcinoma growth

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