Biosynthesis of lex family glycosphingolipids and its gene regulation: XIV.in apoptotic breast carcinoma cells

In human bodies most of the normal cells in their life cycle die through apoptosis (programmed cell death). However, metastatic cancer cells die mostly by Necrosis where, through the cell surface pores, degraded products and newly expressed unfriendly compounds come out and cause death of normal vicinal cells. Apoptotic, or programed cell death of normal cells, is less toxic and is absent in cancer cells to achieve temporary immortality. However, in cancer cells blocked steps of apoptosis can be activated by some chemicals (cis-platin, Betulinic acid, L/-D-PPMP.Tamoxifen, or Melphalan). These chemicals (apoptotic agents) could be called new generation anti-cancer drugs if these can be targeted mostly to the cancer cells of the patients. Apoptotic agents also regulate Glyco-genes in the glycolipid (LeX family) biosynthesis pathway. The Glyco-genes are modulated in cancer cells for the synthesis of hundreds of cell-surface macromolecules (glycoproteins and glycosphingolipids). It is believed that some of these glycoconjugates are involved in the metastasis of cancer cells and could be termed as cancer cell “Markers”. Modulation of the genes (determined by DNA microarray studies) involved in the biosynthesis of these marker glycosphingolipids (GSLs) may be a direct measure of cancer metastasis. Transcriptional expressions (mRNA) of some of these glyco-genes were quantitated by DNA Micro-arrays (containing over 340 glyco-genes attached to the glass cover slips). Within a short induction period (2 to 6 hours) a differential transcriptional regulation was observed. When tested for post-translational activity measurement or post-transcriptional mRNA content (assayed by DNA Micro-array studies), they were found to be regulated differentially. After a longer induction period (24 to 48 hours), all these enzymes were down regulated (less than 10%). Three clonal breast cancer cell lines (SKBR-3, MDA-468, and MCF-7) were used for our studies and the results are reviewed in this article.