Submitted on July 11, 2004 (04-A-160-ASCB) for Presentation at The 44th Annual Meeting of the American Society for Cell Biology, December 4-8, 2004, Washington, DC.

"Reprogramming as an Approach to Neoplasms. " *

Jeannette A. Hovsepian 1, @ and John H. Frenster 2, @

Departments of 1 Radiology and of 2 Medicine, Stanford University School of Medicine, Stanford, California  94305, USA,

@ Present Addresses: RNA Research, Physicians’ Educational Series, Atherton, CA  94027-5446 USA.
Phone:  +1 650 367 6483;   Fax:  +1 650 364 1773;   e-mail:   frenster@euchromatin.net

* Supported in part by a USPHS Research Career Development Award (CA-17857) from the National Cancer Institute to J.H.F.


Abstract:

Although reprogramming of chromatin normally occurs during early telophase, activator RNA exchange can result in chromatin reprogramming during interphase (Frenster JH, and Hovsepian JA, "Activator RNA Exchange during Interphase Chromatin Reprogramming", RNA2004: 305 (2004). Small nuclear RNA species play a role in epigenetic silencing and/or activating of specific genes (Sleutels F, et al, "The Noncoding Air RNA is Required for Silencing Autosomal Imprinted Genes", Nature 415: 820 (2002), and may be necessary for mammalian cells in resisting oncogenic transformation (Takamizawa J, et al, "Reduced Expression of let-7 Micro RNAs in Human Lung Cancer is Associated with Shortened Post-Operative Survival," Cancer Res. 64: 3753 (2004). Many molecular lesions after transformation are DNA-based, including chromosomal amplification, deletion, mutation, and translocation. Epigenetic lesions, not involving DNA sequences directly, are RNA-based, and perhaps amenable to RNA exchange during reprogramming. An interesting experiment by DeCarvalho S., "Effect of  RNA from Normal Human Marrow on Leukaemic Marrow In-Vivo", Nature 197: 1077 (1963) showed that pure isolated RNA from normal bone marrow was able to temporarily reverse the neoplastic state of human acute myelocytic leukemia cells following intra-marrow injection. RNA-based lesions may be more reversible than DNA-based lesions within human neoplasms. http://www.euchromatin.com/RepNeo01.htm .


References:

1. Frenster JH, and Hovsepian JA, "Activator RNA Exchange during Interphase Chromatin Reprogramming", RNA2004: 305 (2004).

2. Sleutels F, Zwart R, and  Barlow DP, "The Noncoding Air RNA is Required for Silencing Autosomal Imprinted Genes", Nature 415: 810 (2002).

3. Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, Harano T, Yatabe Y, Nagino M, Nimura Y, Mitsudomi T, and Takahashi T, "Reduced Expression of let-7 Micro RNAs in Human Lung Cancer is Associated with Shortened Post-Operative Survival," Cancer Res. 64: 3753 (2004).

4. DeCarvalho S. "Effect of  RNA from Normal Human Marrow on Leukaemic Marrow In-Vivo", Nature 197: 1077 (1963) .

5. Reilly KM, Tuskan RG, Christy E, Loisel DA, Ledger J, Bronson RT, Smith CD, Tsang S, Munroe DJ, and Jacks T, "Susceptibility to astrocytoma in mice mutant for Nf1 and Trp53 is linked to chromosome 11 and subject to epigenetic effects", Proc. Natl. Acad. Sci. USA, vol. 101, no. 35, pp. 13008-13013 (August 31, 2004).

Links to RNA and Biological Causality:


Further Topics in:  Euchromatin,  active DNA, and  RNA  ribo-regulators:

Links to Euchromatin Activator RNA Reviews:
Links to Euchromatin Activator RNA Research:
Links to Ultrastructural Probes of DNase I-Sensitive Sites:
Links to RNA as a Therapeutic Agent:
Links to Hodgkin Lymphoma Immuno-Pathology:
Links to Activated T-Lymphocyte Immunotherapy:
Links to Medical Systems Biology:
Links to Selective Gene Transcription:
Links to RNA-Induced Epigenetics:
Links to RNA-Induced Embryogenesis:
Links to RNA and Biological Causality:
Links to Reprogramming and Neoplasia:

A Brief History of Activator RNA:

"Ultrastructural Probes of Active DNA Sites, and the RNA Activators of DNA". (PowerPoint Presentation).


Top of Page - Euchromatin Network - Current Research - Forums - Other Sites - Future Events -


euchromatin: "the most active portion of the genome within the cell nucleus".