کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9092997 1149418 2005 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Tissue-Type Plasminogen Activator Is Upregulated in Metastatic Breast Cancer Cells Exposed to Insulin-Like Growth Factor-I
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیهوشی و پزشکی درد
پیش نمایش صفحه اول مقاله
Tissue-Type Plasminogen Activator Is Upregulated in Metastatic Breast Cancer Cells Exposed to Insulin-Like Growth Factor-I
چکیده انگلیسی
The insulin-like growth factor (IGF) system plays an important role in breast tumorigenesis. Breast cancer cells express the type I IGF receptor (IGF-IR) and respond to IGFs in the environment. Tissue-type plasminogen activator (tPA) has been shown to be associated with neoplastic transformation and the invasive phenotype for highly aggressive tumors; however, its role in breast cancer remains unclear. We asked whether there is a relationship between the IGF system and tPA in estrogen receptor-negative breast cancer cells that could contribute to invasion. When MDA-MB-435s breast cancer cells were exposed to IGF-I, tPA messenger RNA (mRNA) was upregulated in a time-dependent fashion. Tissue-type plasminogen activator protein accumulation was also increased in a similar manner. The invasiveness of MDA-MB-435s cells was enhanced in the presence of IGF-I. When the MDA-MB-435s cells were stably transfected with an antisense IGF-IR expression construct, the transfectants expressed high levels of IGF-IR antisense, dramatically reduced levels of endogenous IGF-IR, and a decrease in relative staining intensity for IGF-IR protein. A marked suppression in tPA mRNA expression occurred in MDA-MB-435s cells accompanying inhibition of IGF-IR. When cells carrying the antisense IGF-IR expression construct were exposed to IGF-I, tPA protein accumulation was significantly lower than that of control transfected cells. To our knowledge, this study is the first to show a relationship between the IGF system and tPA. Strategies that target the IGF/tPA pathway could provide alternative treatments for patients with certain types of metastatic breast cancer.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Clinical Breast Cancer - Volume 6, Issue 4, October 2005, Pages 340-348
نویسندگان
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