عنوان

The role of nuclear IGF-I receptor in diethylstilbestrol (DES)-induced cell proliferation

شماره

TLpq304235020

زبان متن نوشتاري يا گفتاري و مانند آن

انگلیسی

عنوان اصلي

The role of nuclear IGF-I receptor in diethylstilbestrol (DES)-induced cell proliferation

نام عام مواد

[Thesis]

نام نخستين پديدآور

C.-W. Chen

نام ساير پديدآوران

D. Roy

نام ناشر، پخش کننده و غيره

The University of Alabama at Birmingham

تاریخ نشرو بخش و غیره

1996

نام خاص و کميت اثر

138

جزئيات پايان نامه و نوع درجه آن

Ph.D.

کسي که مدرک را اعطا کرده

The University of Alabama at Birmingham

امتياز متن

1996

متن يادداشت

Estrogens are carcinogenic to both rodents and humans. In animals, stilbene estrogen, diethylstilbestrol (DES) acts as both initiator and promotor. The mechanism by which DES influences proliferation of normal and transformed cells is not clear. The objective of the present research was to investigate the role of nuclear insulin-like growth factor-I receptor (nIGF-IR) in estrogen-induced cell proliferation. It is proposed that acute exposure to animals with DES leads to overexpression of nlGF-IRs, which provides stimuli for uncontrolled cell proliferation in the target organ of carcinogenesis (Syrian hamster kidney). For the first time, the presence of IGF-IR on the nucleus of hamster renal epithelial cells was detected by binding assay, affinity labeling and Western blotting assays. And the nuclear localization of IGF-IRs was confirmed by immunofluorescence staining. The DES-stimulated nIGF-IR in nuclei was demonstrated by receptor binding, affinity labeling and Western blotting assays. It was observed that DES exerted both dose- and time-dependent increases on renal epithelial cell proliferation. In addition, the DES treatment also enhanced IGF-IR gene expression. Pretreatment of an antiestrogenic compound, ICI182780, strongly attenuated the DES-stimulated cell proliferation, and also inhibited the DES-induced IGF-IR gene expression. Moreover, cotreatment of cells with an anti-IGF-IR antibody (usd\alphausdIR3) significantly attenuated the growth-stimulatory effects of DES. The receptor binding assay revealed that nuclear usd\rm \lbrack \sp{125}I\rbrackusdIGF-I specific binding was doubled by DES treatment. Cotreatment of cells with a plant flavone, luteolin, and DES resulted in a 78% reduction in cell growth compared to DES alone. DES-induced IGF-I receptor gene expression was effectively attenuated by the presence of luteolin. Moreover, the nuclear tyrosine kinase activity was also inhibited in a dose-dependent manner by luteolin. These findings suggested that the up-regulation of nIGF-IR coupled with enhanced cell proliferation by short term exposure of DES may play an important role in the induction of estrogen-induced carcinogenesis.

موضوع مستند نشده

Cell proliferation

موضوع مستند نشده

Diethylstilbestrol

موضوع مستند نشده

Health and environmental sciences

موضوع مستند نشده

insulin like growth factor I

موضوع مستند نشده

Nuclear IGF-I receptor

موضوع مستند نشده

Toxicology

مستند نام اشخاص تاييد نشده

C.-W. Chen

مستند نام اشخاص تاييد نشده

D. Roy

نام الکترونيکي

فرمت انتشار

p

نوع ماده

[Thesis]

کد کاربرگه

276903

سطح دسترسي

a

تكميل شده

Y