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Rich66 · 10-31-2009, 01:49 PM

Molecular Diagnostics

British Journal of Cancer (2009) 101, 1613–1619. doi:10.1038/sj.bjc.6605336 www.bjcancer.com
Published online 22 September 2009
Melatonin inhibits aromatase promoter expression by regulating cyclooxygenases expression and activity in breast cancer cells

C MartÃ*nez-Campa¹, A GonzÃ¡lez¹, M D Mediavilla¹, C Alonso-GonzÃ¡lez¹, V Alvarez-GarcÃ*a¹, E J SÃ¡nchez-BarcelÃ³¹ and S Cos¹
¹Department of Physiology and Pharmacology, School of Medicine, University of Cantabria, 39011 Santander, Spain
Correspondence: Dr S Cos, Departamento de FisiologÃ*a y FarmacologÃ*a, Facultad de Medicina, Universidad de Cantabria, Cardenal Herrera Oria s/n, 39011 Santander, Spain. E-mail: coss@unican.es
Received 29 May 2009; Revised 19 August 2009; Accepted 1 September 2009; Published online 22 September 2009.

Top of pageAbstract

Background:

Melatonin reduces the development of breast cancer interfering with oestrogen-signalling pathways, and also inhibits aromatase activity and expression. Our objective was to study the promoters through which melatonin modifies aromatase expression, evaluate the ability of melatonin to regulate cyclooxygenases and assess whether the effects of melatonin are related to its effects on intracellular cAMP, in MCF-7 cells.

Methods:

Total aromatase mRNA, aromatase mRNA promoter regions and cyclooxygenases mRNA expression were determined by real-time RT–PCR. PGE₂ and cAMP were measured by kits.

Results:

Melatonin downregulated the gene expression of the two major specific aromatase promoter regions, pII and pI.3, and also that of the aromatase promoter region pI.4. Melatonin 1 nM was able to counteract the stimulatory effect of tetradecanoyl phorbol acetate on PGE₂ production and inhibit COX-2 and COX-1 mRNA expression. Melatonin 1 nM elicited a parallel time-dependent decrease in both cyclic AMP formation and aromatase mRNA expression.

Conclusions:

This study shows that melatonin inhibits aromatase activity and expression by regulating the gene expression of specific aromatase promoter regions. A possible mechanism for these effects would be the regulation by melatonin of intracellular cAMP levels, mediated by an inhibition of cyclooxygenase activity and expression.

Keywords:

melatonin, pineal, MCF-7 cells, breast cancer, aromatase

10-31-2009, 01:49 PM	#12
Rich66 Senior Member Join Date: Feb 2008 Location: South East Wisconsin Posts: 3,431	Re: Melatonin cancer treatment biology etc Molecular Diagnostics British Journal of Cancer (2009) 101, 1613–1619. doi:10.1038/sj.bjc.6605336 www.bjcancer.com Published online 22 September 2009 Melatonin inhibits aromatase promoter expression by regulating cyclooxygenases expression and activity in breast cancer cells C MartÃnez-Campa¹, A GonzÃ¡lez¹, M D Mediavilla¹, C Alonso-GonzÃ¡lez¹, V Alvarez-GarcÃa¹, E J SÃ¡nchez-BarcelÃ³¹ and S Cos¹ ¹Department of Physiology and Pharmacology, School of Medicine, University of Cantabria, 39011 Santander, Spain Correspondence: Dr S Cos, Departamento de FisiologÃa y FarmacologÃa, Facultad de Medicina, Universidad de Cantabria, Cardenal Herrera Oria s/n, 39011 Santander, Spain. E-mail: coss@unican.es Received 29 May 2009; Revised 19 August 2009; Accepted 1 September 2009; Published online 22 September 2009. Top of pageAbstract Background: Melatonin reduces the development of breast cancer interfering with oestrogen-signalling pathways, and also inhibits aromatase activity and expression. Our objective was to study the promoters through which melatonin modifies aromatase expression, evaluate the ability of melatonin to regulate cyclooxygenases and assess whether the effects of melatonin are related to its effects on intracellular cAMP, in MCF-7 cells. Methods: Total aromatase mRNA, aromatase mRNA promoter regions and cyclooxygenases mRNA expression were determined by real-time RT–PCR. PGE₂ and cAMP were measured by kits. Results: Melatonin downregulated the gene expression of the two major specific aromatase promoter regions, pII and pI.3, and also that of the aromatase promoter region pI.4. Melatonin 1 nM was able to counteract the stimulatory effect of tetradecanoyl phorbol acetate on PGE₂ production and inhibit COX-2 and COX-1 mRNA expression. Melatonin 1 nM elicited a parallel time-dependent decrease in both cyclic AMP formation and aromatase mRNA expression. Conclusions: This study shows that melatonin inhibits aromatase activity and expression by regulating the gene expression of specific aromatase promoter regions. A possible mechanism for these effects would be the regulation by melatonin of intracellular cAMP levels, mediated by an inhibition of cyclooxygenase activity and expression. Keywords: melatonin, pineal, MCF-7 cells, breast cancer, aromatase __________________ Mom's treatment history (link)