Identification of Pro-Differentiation p53 Target Genes and Evaluation of Expression in Normal and Malignant Mammary Gland
DARTMOUTH COLL HANOVER NH
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Delta-N-p63 plays a critical role in making decision to preserve or forfeit mammary stem cellsprogenitor cells self-renewal capacity. In embryonic stem cells, some transcription factors including oct34, nanog, c-myc and Klf-4 are critical to maintain self-renewal and multi-potential stasis. Our study revealed that these key transcription factors also exist in adult mammary stem cellsprogenitor cells as well as breast cell lines such as IMEC, MCF-10A, SUM102 and MCF- 7 cells. Over-expression of ectopic delta-N-p63 could inhibit the proliferation rate of treated cells, and had diverse regulation effects on transcript level of oct34, nanog, c-myc and Klf-4 in infected breast cell lines. Retinoic acid treatment also could slow down the growth of treated beast cells, and change the transcript level of these self-renewal related genes. Both of RA treatment and over-expression of delta-N-p63 could increase mammosphere formation capacities in most breast cell lines including IMEC, SUM102 and MCF-7 cells. The mRNA level of oct34 and nanog was detectable in mouse mammary stem cells or progenitor cells enriched subpopulation. Additionally, both oct34 and nanog transcript level could be regulated by over-expression or removal of delta- N-p63 in mammary stem cells or progenitors fractions, respectively. In human breast cell lines such as SUM102 cells, over-expression of mouse oct34 and nanog could increase the mammosphere numbers significantly. On the other hand, removal of delta-N-p63 in MCF-10A cells could decrease the mammosphere formation capacity dramatically. Taken together, all these findings strongly suggested there might be correlation between delta-N-p63 and ES programming genes including oct34, nanog, c-myc and Klf-4 to regulate stem cell self-renewal and sustaining of pluripotency in adult mammary gland.
- Anatomy and Physiology
- Medicine and Medical Research