Aberrant expression of epidermal growth factor receptor in aural cholesteatoma

Bujía, J; Holly, Anja; Schilling, V.; Negri, B.; Pitzke, P.; Schulz, Peter

doi:10.1288/00005537-199303000-00015

Cited by 42 publications

(31 citation statements)

References 20 publications

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“…EGF has been shown to act as a mitogen as well as a differentiation factor for many cell types (Bonassar & Trippel 1997). It is present in the circulation at very low concentrations that, nevertheless, also elicit cellular responses in vitro (Bujia et al 1993, Murakami et al 1994. In addition, the kidney is thought to be the major site of EGF synthesis in mammals (Fisher et al 1989).…”

Section: Introductionmentioning

confidence: 99%

The effect of epidermal growth factor and IGF-I infusion on hepatic and renal expression of the IGF-system in adult female rats

Neck

Berghout²,

Vinter‐Jensen³

et al. 2000

Journal of Endocrinology

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Systemic administration of epidermal growth factor (EGF) in neonatal rats results in reduced body weight gain and decreased circulating levels of IGF-I, suggesting its involvement in EGF-induced growth retardation.We investigated the effect of EGF and/or IGF-I administration for 7 days on circulating IGF-I and IGFBP levels and hepatic and renal IGF-system mRNA expression profiles in adult female rats. EGF administration (30 µg/rat/day) did not influence body weight, liver or kidney weight. In contrast, IGF-I (400 µg/rat/day) and EGF/IGF-I administration increased both body weight and kidney weight. Also, serum IGF-I and the 30 kDa IGFBPs (IGFBP-1 and -2) were significantly increased in these groups. Serum IGFBP-3 levels increased in the IGF-I group along with increased hepatic IGFBP-1 and -3 mRNA levels. In contrast, in the EGF administration group serum IGFBP-3 levels were significantly decreased; however, the mRNA levels remained unchanged. In the EGF/IGF-I administration group, serum IGF-I and IGFBP-3 levels were significantly lowered when compared with the IGF-I administration group. This was in contrast to the effect on kidney weight increase that was identical for the IGF-I and EGF/IGF-I groups. The decrease in serum IGFBP-3 was not reflected at the hepatic IGFBP-3 mRNA level. IGFBP-3 expression might be regulated at a post-transcriptional level although EGF induced IGFBP-3 proteolysis could not be demonstrated in vitro.We conclude that EGF administration reduced serum IGFBP-3 whereas IGF-I administration increased the level of IGFBP-3 and IGF-I and resulted in an increased body and kidney weight in adult female rats.

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Section: Introductionmentioning

confidence: 99%

The effect of epidermal growth factor and IGF-I infusion on hepatic and renal expression of the IGF-system in adult female rats

Neck

Berghout²,

Vinter‐Jensen³

et al. 2000

Journal of Endocrinology

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“…Interleukin-1 stimuliert im Rahmen der Wundheilung die Fibroblastenproliferation, die ebenfalls in der Perimatrix des Cholesteatoms nachweisbar ist [25,34]. Zusätzlich könnten Il-1 und TGF-α als autokrine Wachstumsfaktoren auf die Keratinozyten des Cholesteatomepithels, nicht aber an den Epithelzellen der Mittelohrschleimhaut wirken [4,28]. Die fehlende Immunreaktivität für den EGF-R ist ein Hinweis darauf, daß die angrenzende Mittelohrschleimhaut nicht auf das lokal freigesetzte EGF und TGF-α reagieren kann.…”

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Immunhistochemische Untersuchungen von Mittelohrschleimhautresten im Cholesteatom

Sudhoff

Borkowski

Bujía

et al. 1997

HNO

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The development of a middle ear cholesteatoma is usually associated with chronic inflammation and displacement of the mucosa present by the invading squamous epithelium. To analyze the clinically different behaviors of both epithelia, we used immunohistochemical methods to study the distribution and expression of interleukin-1 (Il-1), transforming growth factor-alpha (TGF-alpha), epidermal growth factor (EGF), epidermal growth factor-receptor (EGF-R), the proliferation marker MIB 1, c-myc proto-oncogene product and activation marker 4F2. Results stromal that keratinocytes in a cholesteatoma exhibited a much higher activation and proliferation rate when compared to middle ear mucosa cells. Middle ear epithelial cells showed no immunoreactivity for TGF-alpha, EGF-R, Il-1 and c-myc in contrast to the markedly positive immunoreactivity found in cholesteatoma matrix. The local release of cytokines and growth factors, such as TGF-alpha, EGF and Il-1 by inflammatory cells seems to be an important factor for the hyper-proliferative behavior of cholesteatoma epithelium. Our findings could contribute to the pathogenesis of middle ear cholesteatoma and give a possible explanation for the sustained progression of its growth leading to displacement of the middle ear mucosa.

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“…The presence of p27 protein was observed in 35.7% of cholesteatoma and 83.5% of EECS. Accumulation of keratin debris in the middle ear is a characteristic of cholesteatoma and is the result of the increased rate of keratinocyte death [1][2][3]16] . The increase of epithelium proliferation in cholesteatoma may be caused by decreased activity of CDK inhibitor (p27).…”

Section: Discussionmentioning

confidence: 99%

“…All types of cholesteatoma were composed of basal, spinous and granular cells layers of squamous cell epithelium (matrix), desquamated epithelial cells and stroma (perimatrix) [1] . Most of acquired cholesteatomas are the result of migration of the squamous cell epithelium into the tympanic cavity [1][2][3] . This process is caused by: hyperproliferation of epithelium in the flaccid part of the tympanic membrane, invagination of the retraction pockets into the tympanic cavity, ingrowing of epithelial cells of the external auditory meatus or tympanic membrane through the tympanic membrane perforation, mechanical or surgical injuries or squamous cell metaplasia of the middle ear [1,3,4] .…”

Section: Introductionmentioning

confidence: 99%

Cell Cycle Inhibitory Protein p27 in Human Middle Ear Cholesteatoma

Kuczkowski

Bakowska²,

Pawełczyk³

et al. 2006

ORL

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Aim: To evaluate the immunohistochemical and molecular presentation of protein p27 in cholesteatoma. Methods: 42 cholesteatoma samples and 6 external ear canal skin (EECS) specimens were investigated and analyzed taking into consideration congenital, acquired, recurrent cholesteatoma, and EECS. Results: The expression of p27 was found in 16 (38.1%) out of 42 specimens of cholesteatoma and in 5 (83.3%) out of 6 specimens of EECS. There was a significant difference in p27-positive staining rate between EECS and cholesteatoma epithelium (p < 0.008). The presence of p27 was detected in 10 cases of acquired cholesteatoma, 2 cases of congenital and 3 cases of recurrent cholesteatoma. There was no significant difference between the presence of p27 in cholesteatoma and EECS (p = 0.01). Conclusion: The down-regulation of p27 is a key player in cell cycle control and plays an undefined role in the pathogenesis of all types of cholesteatoma.

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Aberrant expression of epidermal growth factor receptor in aural cholesteatoma

Cited by 42 publications

References 20 publications

The effect of epidermal growth factor and IGF-I infusion on hepatic and renal expression of the IGF-system in adult female rats

The effect of epidermal growth factor and IGF-I infusion on hepatic and renal expression of the IGF-system in adult female rats

Immunhistochemische Untersuchungen von Mittelohrschleimhautresten im Cholesteatom

Cell Cycle Inhibitory Protein p27 in Human Middle Ear Cholesteatoma

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