Possible co-regulation of genes associated with enhanced progression of mammary adenocarcinomas.
Tumor progression is a multistep process in which alterations in the expression of numerous gene products may give rise to highly malignant cellular variants. In the present study, we analyzed the differential expression of several genes in cellular variants of mammary adenocarcinomas with high or low malignancy potential, which originated in a common ancestor. To assess the generality of our findings, high and low malignancy variants were derived from two different mammary adenocarcinoma cell lines, namely DA3 and CSML cells. Of major importance is the fact that the differences between high- and low-malignancy variants observed in one system of mammary adenocarcinoma cells (DA3 cells) were identically reproduced in the other system of mammary adenocarcinoma cells (CSML cells). The high malignancy variants of tumors both DA3-high and CSML-high (previously called CSML-100), expressed higher levels of factors that induce monocyte migration than the low malignancy DA3-low and CSML-low (previously called CSML-0) variants. In addition, it was found that DA3-high and CSML-high cell variants expressed higher levels of monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) and matrix metalloproteinases (MMPs) than the low malignancy variants (DA3-low and CSML-low). These results suggest that MCP-1, IL-6 and MMPs potentially contribute to mammary adenocarcinoma progression and that their expression is regulated by a common pathway. The expression of MCP-1, IL-6 and MMPs in both DA3-high and CSML-high cells was up-regulated by tumor necrosis factor alpha (TNFalpha). The fact that TNFalpha exerted similar effects on the expression of these three factors in both cell systems raises the possibility of a coordinated co-regulation of tumor-promoting factors.
Neumark
E
E
Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences and The Ela Kodesz Institute for Research on Cancer Development and Prevention, Tel-Aviv University, Tel-Aviv, Israel.
Cohn
M A
MA
Lukanidin
E
E
Witz
I P
IP
Ben-Baruch
A
A
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000096:biosynthesis; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D015674:Mammary Neoplasms, Animal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D009000:Monocytes / Q000502:physiology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
D018932:Chemokine CCL2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D020782:Matrix Metalloproteinases