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Iodine and the Body

 

Iodine and the Breast  

Natarajan

 

Role of lipoxygenases in breast cancer.

Natarajan R, Nadler J.

Front Biosci. 1998 Jun 8;3:E81-8. Review.

[abstract only]

 

"The interaction of growth factors such as epidermal growth factor (EGF) with their receptors on breast cancer cells can lead to the hydrolysis of phospholipids and release of fatty acids such as arachidonic acid which can be further metabolized by the lipoxygenase (LO) pathway. Several LO products have been shown to stimulate oncogenes and have mitogenic and chemotactic effects. The 12-LO product, 12-hydroxyeicosatetraenoic acid (12(S)HETE), has been shown to play a key role in mediating several steps of the process of hematogenous metastasis and tumor cell adhesion. 12-LO can also be activated by several growth factors and inflammatory cytokines. A growing body of evidence suggests that specific metabolites of arachidonic and/or linoleic acid serve as central elements in signal pathways necessary for cell mitogenesis as induced by growth factors or oncogenic transformation. This review examines the role of LOs in breast cancer. The growth of breast cancer cells has been shown to increased by certain LO products and, LO pathway inhibitors could block the growth of some breast cancer cells. 12-LO activity and expression was increased in breast cancer tissues relative to the uninvolved normal tissue, and also in cultured breast cancer cells relative to normal breast cells. Treatment of the breast cancer cell line, MCF-7 cells, with epidermal growth factor (EGF), led to significant increases in 12-LO activity and expression. Thus, activation of the 12-LO pathway may play a key role in basal and EGF-induced breast cancer cell growth."

 

 

Increased 12-lipoxygenase expression in breast cancer tissues and cells. Regulation by epidermal growth factor.

Natarajan R, Esworthy R, Bai W, Gu JL, Wilczynski S, Nadler J.

J Clin Endocrinol Metab. 1997 Jun;82(6):1790-8.

 

"The interaction of growth factors, such as epidermal growth factor (EGF) with their receptors, on breast cancer cells can lead to the hydrolysis of phospholipids and release of fatty acids, such as arachidonic acid, which can be further metabolized by the lipoxygenase (LO) pathway. Several LO products have been shown to stimulate oncogenes and have mitogenic and chemotactic effects. In this study, we have evaluated the regulation of 12-LO activity and expression in breast cancer cells and tissues. Leukocyte-type 12-LO messenger RNA (mRNA) expression was studied by a specific RT-PCR method in matched, normal, uninvolved and cancer-involved breast tissue RNA samples from six patients. In each of these six patients, the cancer-involved section showed a much higher level of 12-LO mRNA than the corresponding normal section. 12-LO mRNA levels also were greater in two breast cancer cell lines, MCF-7 and COH-BR1, compared with the nontumorigenic breast epithelial cell line, MCF-10F. The growth of the MCF-7 cells was significantly inhibited by two specific LO blockers but not by a cyclooxygenase blocker. Treatment of serum-starved MCF-7 cells with EGF for 4 h led to a dose-dependent increase in the formation of the 12-LO product, 12-hydroxyeicosatetraenoic acid. EGF treatment also increased the levels of the leukocyte-type 12-LO protein expression at 24 h. These results suggest that activation of the 12-LO pathway may play a key role in basal and EGF-induced breast cancer cell growth."
 

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