Cidofovir modulated gene expression in recurrent respiratory papillomatosis.
OBJECTIVE
Recurrent respiratory papillomatosis (RRP) is a benign aerodigestive tract neoplasm. Cidofovir, an antiviral drug, has demonstrated efficacy in slowing and/or reducing RRP recurrence. This investigation examined the differential gene expression of RPP before and after cidofovir use in vivo.


METHODS
Papillomas were harvested from two patients pre- and post-cidofovir treatment. RNA was extracted from the tissues and separate Serial Analysis of Gene Expression (SAGE) libraries created. Overall gene expression as well as relative gene expression in the four libraries was compared.


RESULTS
Over 19,000 tags were found in each of the libraries, with over 6000 unique transcripts identified in the pre-treatment and over 6000 identified in the post-cidofovir libraries of both patient 1 and 2. Following cidofovir treatment, the greatest up-regulation was in gene families associated with cell proliferation, metabolism, transport and response to biotic stimuli. Post-treatment up-regulation was seen in numerous specific genes, such as Interferon Regulatory Factor 7 (P=0.000014), which has been associated with virus-host interactions, passive viral induction of host immune response, and response to DNA damage stimulus. Down-regulation was demonstrated in gene families associated with transcription, regulation of nucleic acid metabolism, and signal transduction.


CONCLUSIONS
Creation of RRP SAGE libraries demonstrates a broad list of genes expressed in RRP, as well as significant differences in gene expression after exposure to cidofovir, potentially allowing for a more thorough understanding of important genetic pathways in RRP treatment. In addition, over 1400 unique transcripts were identified, which will facilitate new gene discovery in RRP research.
Poetker
David M
DM
Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI 53226, United States.
Patel
Nalin J
NJ
Kerschner
Joseph E
JE
D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D015536:Down-Regulation; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D050839:Interferon Regulatory Factor-7 / Q000235:genetics; D063065:Organophosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D010212:Papilloma / Q000188:drug therapy / Q000821:virology*; D012367:RNA, Viral / Q000032:analysis; D012008:Recurrence; D012142:Respiratory Tract Neoplasms / Q000188:drug therapy / Q000821:virology*; D015854:Up-Regulation
D000998:Antiviral Agents; D050839:Interferon Regulatory Factor-7; D063065:Organophosphonates; D012367:RNA, Viral; D003596:Cytosine; D000077404:Cidofovir