Epidermal growth factor and transforming growth factor .alpha. bind differently to the epidermal growth factor receptor

Winkler, Moritz; O’Connor, Lynn H.; Winget, Marcy; Fendly, Brian M.

doi:10.1021/bi00441a033

Cited by 128 publications

(64 citation statements)

References 26 publications

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“…It was also of interest to note that there was no difference in the TGFa levels between BPH and prostate cancers even though there was a marginal increase in TGFo expression as the tumour became less differentiated. Significantly however, this increase in TGFa concentrations was manifested at a time when the expression of the EGF-receptor is down regulated (Maddy et al, 1989) thus raising further the possibility that TGFa may be excerting its biological effects by interacting with receptor sites other than those associated with EGF (Winkler et al, 1989). Although one should not exclude the possibility that higher levels of EGF-R activation can also result in more rapid receptor turnover and/or down regulation of receptor expression.…”

Section: Resultsmentioning

confidence: 98%

Epidermal growth factor and transforming growth factor α concentrations in BPH and cancer of the prostate: their relationships with tissue androgen levels

Yang

Chisholm²,

Habib³

1993

Br J Cancer

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(Gleason, 1977). The remainder of the tissue was snap frozen in liquid nitrogen and finally pulverised in a micro-dismembrator (Braun AG, Melsungen, Germany). The powdered tissue was then lyophilised to dryness and stored at -70°C until needed. For growth factor studies 70 mg of the lyophilised material was used whereas only 50 mg were required for steroid measurements.Extraction of growth factors Lyophilised samples were resuspended in 1 ml buffer (50 mmol 1 Tris, 5 mol 1' of phenyl-methylsulphonyl fluoride, 2 mmol I 1' of EDTA pH 7.4) containing 1,000 counts of either '251I-EGF or '25I-TGFx to monitor manipulative losses. The samples were homogenised with a glass/glass Dounce Homogeniser and left on ice for 1 h to equilibrate. The homogenates were then centrifuged, the supernatants saved and the resultant pellets were resuspended in 2 ml of enzyme mixture (230 U ml-' of collagenase, 125 U ml-' of hyaluronidase in 150 mmol 1' of NaCI) and incubated overnight at 37C; these conditions were found to be optimal and ensured maximum growth factor recovery. The digested pellets were subsequently sonicated (six cycles of 20s with 1 min cooling interval at an amplitude of 22 ,; MSE soniprep 150) the resultant mixture was centrifuged as before, the supernatant saved and the pellet was resuspended in 2 ml Tris buffer. Homogenisation, centrifugation and resuspension were then repeated twice with the supernatants always being saved. The supernatants were then pooled and the recoveries were assessed. The mean recovery of '251I-EGF added at the beginning of the extraction procedure was 72 ± 6% whilst that of 125I-TGFo was 69 ± 8%. The. supernatants were finally snap frozen, lyophilised to dryness and stored at -700 until required.

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Section: Resultsmentioning

confidence: 98%

Epidermal growth factor and transforming growth factor α concentrations in BPH and cancer of the prostate: their relationships with tissue androgen levels

Yang

Chisholm²,

Habib³

1993

Br J Cancer

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“…Although TGF-a belongs to the EGF family and has 40% sequence homology with EGF (17), it was not as effective as EGF in increasing the blastocyst cell numbers. This is not surprising, since EGF and TGF-a bind differently to EGF receptors (18). This may explain differences in the potency of expressing biological activities of these two related growth factors (19)(20)(21)(22)(23).…”

Section: Discussionmentioning

confidence: 99%

Preimplantation embryo development in vitro: cooperative interactions among embryos and role of growth factors.

Paria

Dey

1990

Proc. Natl. Acad. Sci. U.S.A.

586

372

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We have established a model that shows cooperative interaction among preimplantation embryos and the role of growth factors on their development and growth.Two-cell mouse embryos cultured singly in 25-ed microdrops had inferior development to blastocysts and lower cell numbers per blastocyst compared with those cultured in groups of 5 or 10. The inferior development of singly cultured embryos was markedly improved by addition of epidermal growth factor (EGF) or transforming growth factor a or 31 (TGF-a or TGF-131) to the culture medium. The stage of embryonic development, primarily affected by these treatments, was between eight-cell/morula and blastocyst. Furthermore, bIastocysts developed from eight-cell embryos cultured in groups or singly in the presence ofEGF showed a higher incidence ofzona hatching compared with those cultured singly in the absence of EGF. (P4) and estrogen (E) reverses these defects (1, 2). These observations suggest that although certain factors of embryonic origin participate in an autocrine regulation of embryonic development, the full complement of preimplantation embryo development requires additional paracrine factors that originate from the reproductive tract under the influence of P4 and E. There is no convincing evidence for direct effects of P4 and/or E on preimplantation embryo development. The concept of autocrine regulation of preimplantation embryo development and differentiation is further supported by the fact that preimplantation embryos can develop into blastocysts in vitro in a simple medium (3). However, embryonic growth rate is slower in vitro and there are fewer cells in in vitro-grown blastocysts (4). This suggests that absence of growth factors of reproductive tract origin and/or dilution of these factors released by the embryos in the culture medium are responsible for retarded development of preimplantation embryos in vitro. This contention is further supported by recent reports of synthesis of several growth factors by the preimplantation embryo (5) and the uterus (6-8). Thus growth factors produced by the preimplantation embryo and/or the reproductive tract are available to influence embryonic development and function in an autocrine/paracrine manner. If growth factors produced by the preimplantation embryo act on them, then it can be postulated that preimplantation embryos cultured in a small number in a defined volume of culture medium will show inferior development compared with those cultured as a large group. This could reflect a greater dilution of the growth factors secreted from a small number of cultured embryos into the medium compared with those cocultured in a larger group. This inferior development should then be corrected by addition of growth factors in the culture medium. To test this hypothesis, we have developed a unique model to examine the cooperative interaction among embryos and the role of growth factors and their interactions on preimplantation embryo development in vitro.

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“…Although TGF-c~ and EGF exert similar effects in many systems, TGF-ct appears to be more potent than EGF in terms of Ca z+ release (33,34), prostaglandin synthesis in vascular endothelial cells (35), and an increase in arterial blood flow (36) and in angiogenesis (37). However, differences in the binding of EGF and TGF-ot to EGFR may alter the biological activities (38). TGF-c~ is a 50-amino acid polypeptide derived from a 160-amino acid transmembrane precursor by specific proteolytic cleavage (39).…”

Section: Discussionmentioning

confidence: 99%

Expression of transforming growth factor alpha (TGF-α) gene in mouse embryonic development

Harada

Fujikawa

Yoshida

et al. 1997

J Assist Reprod Genet

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Epidermal growth factor and transforming growth factor .alpha. bind differently to the epidermal growth factor receptor

Cited by 128 publications

References 26 publications

Epidermal growth factor and transforming growth factor α concentrations in BPH and cancer of the prostate: their relationships with tissue androgen levels

Epidermal growth factor and transforming growth factor α concentrations in BPH and cancer of the prostate: their relationships with tissue androgen levels

Preimplantation embryo development in vitro: cooperative interactions among embryos and role of growth factors.

Expression of transforming growth factor alpha (TGF-α) gene in mouse embryonic development

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