From: Stem cells, senescence, neosis and self-renewal in cancer
Transient stem cell properties of Raju cells: |
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   1. Short cell cycle duration of nascent Raju cells (before they undergo first mitosis) – an indication of lack of G1 phase? [5, 6]. |
   2. Reactivation of telomerase conferring extended mitotic life span [139-141]. |
   3. Is it possible to expand Raju cell population without differentiation under proper culture conditions such as EGF or FGF2 [43, 144-148]. |
   4. Increase in cell size accompanied by increase in cell cycle duration-introduction of G1 phase in the cell cycle [Rajaraman, unpublished; 143]. |
   5. Resistance to genotoxins – Expression of multidrug resistance genes? [192, 193]. |
   6. Are they transiently expressing tissue stem cell specific surface markers? (e.g., CD34+ for hematopoietic cells [8]; CD133+ for brain cells [12, 13], CD44+, CD33-, LowLin- for breast cells [9-11]; CD20+ for skin cells [40]; CD44+,α 2β 1hi/CD133+ for prostate cancer cells [41]. |
   7. Are they transiently expressing stem cell specific growth genes? (E.g. Nanog, Oct-4, Wnt, Bmi1 etc.) [188-191] |
   8. Potential to differentiate, although aberrantly. |
Somatic cell properties of mitotic derivatives of Raju cells: |
   1. Resumption of symmetric mitotic division. |
   2. Increase in cell size – Introduction of G1 phase in the cell cycle? [143]. |
   3. Progressive, but, aberrant differentiation. |
   4. Loss of tissue specific stem cell surface markers due to differentiation during extended mitotic proliferation? |
   5. Loss of expression of stem cell specific self-renewal genes? |
   6. Loss of expression of multidrug resistance genes? |
   7. They are subject to aging and associated senescence brought about by telomere attrition. |
   8. Therefore, they have limited division potential. |
   9. Telomere attrition, chromosome breakage-fusion-bridge cycle or genetic stress will result in senescent phase with MN/PG formation, mitotic crisis, and mitotic catastrophe. |
   10. Absence of senescent check points constitutes a built-in mechanism for accumulation of additional mutations via breakage-fusion-bridge cycle, setting in motion the next cycle of S/T-neosis [66, 67]. |