Journal Article

Novel retinoblastoma binding protein RBBP9 modulates sex-specific radiation responses <i>in vivo</i>

Scott Cassie, Igor Koturbash, Darryl Hudson, Mike Baker, Yaroslav Ilnytskyy, Rocio Rodriguez-Juarez, Edgar Weber and Olga Kovalchuk

in Carcinogenesis

Volume 27, issue 3, pages 465-474
Published in print March 2006 | ISSN: 0143-3334
Published online November 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi261
Novel retinoblastoma binding protein RBBP9 modulates sex-specific radiation responses in vivo

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Retinoblastoma (RB) tumor suppressor is a key regulator of apoptosis, a central mediator of the proliferative block induced by ionizing radiation (IR) and a binding target for a variety of proteins that regulate its activity. One of the recently discovered and the least investigated of these is the novel Rb-binding protein RBBP9/BOG. We studied the effects of acute and chronic low dose radiation (LDR) exposure on the induction of RBBP9 and RB signaling pathway in vivo in mouse spleen and found that RBBP9 played a pivotal role in IR responses in vivo. We observed that chronic LDR exposure led to a significant increase of RBBP9 expression in males and a significant decrease in females. Elevated RBBP9 expression in males was paralleled by a pronounced dephosphorylation of RB and a significant drop of PCNA and cyclin A expression. On the contrary, chronic exposure in females led to decreased levels of RBBP9 and increased levels of hyperphosphorylated RB (ppRB) in spleen. Decreased levels of ppRB in spleen of chronically exposed males were correlated with strongly elevated apoptotic rates. In females, the radiation-induced increase of apoptotic index was much less pronounced. Quite surprisingly, the observed sex-specific signaling changes did not result in the sex-specificity of cellular proliferation. The molecular mechanisms and possible repercussions of the radiation-induced sex differences in cellular proliferation and apoptosis are discussed.

Keywords: IR, ionizing radiation; LDR, low dose radiation; RB, retinoblastoma

Journal Article.  6106 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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