Evidence of a field effect associated with mammary cancer chemoprevention by methylseleninic acid.
In the present study, the molecular effects of methylseleninic acid in cancer chemoprevention was evaluated using two closely related sets of targets. The first approach examined the modulation of biomarkers in pathologically-defined premalignant lesions of the rat mammary gland. The second approach involved the use of cDNA microarray technology to characterize the profile of gene expression changes in the whole mammary tissue. Treatment with methylseleninic acid led to quantifiable changes in the expression of selective cell cycle and apoptosis regulatory proteins in the premalignant lesions. The biomarkers in the panel included cyclin A, cyclin D1, p21, p27, bcl-2 and bax. These were found to be modulated in a manner that was consistent with a reduction in the development of premalignant lesions by methylseleninic acid. Microarray analysis using RNA isolated from the whole mammary gland provided highly suggestive clues that methylseleninic acid was able to produce a widespread effect on gene expression in adipocytes and stromal cells, which are present in abundance in the mammary tissue. Thus, epithelial cells may not be the only targets for the action of selenium, even though the focus of selenium chemoprevention is to inhibit premalignant lesions and cancers arising from the epithelial cells. In view of the fact that adipocytes and stromal cells are known to play an important role in the growth and differentiation of their neighboring epithelial cells, the concept of a field effect in selenium chemoprevention is proposed as a new frontierforfuture research endeavors.
Dong
Yan
Y
Department of Experimental Pathology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Ip
Clement
C
Ganther
Howard
H
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D020411:Oligonucleotide Array Sequence Analysis; D016566:Organoselenium Compounds / Q000494:pharmacology*; D011230:Precancerous Conditions / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D016566:Organoselenium Compounds; C008493:methylselenic acid