Proliferation-associated nuclear phosphoproteins are important to study because they may lead to new insights into cell growth and division, and may offer new means to establish prognosis in cancer. pp35 and pp32 are recently identified phosphorylated nuclear proteins whose expression increases nearly ten-fold as resting B lymphocytes are driven to proliferate (1, Appendix I). pp35 mRNA expression is confined to a narrow window around the Gl-S boundary in normal cells, whereas neoplastic cells express pp35 mRNA and protein constitutively. Partial cDNA sequence of pp35 does not match any previously published sequence. Discovered in lymphoid cells, pp35 and pp32 or related proteins are present immunohistochemically in certain epithelial and mesenchymal cells. Preliminary clinical studies in paraffin-embedded human tissue show that the frequency of positive cells and the intensity of expression both increase along a spectrum from normal lymph node to high grade lymphoma. Epithelial lesions exhibit similar changes. The major questions asked by this study are whether pp35 and pp32 in normal tissues represent the same molecular form found neoplastic tissues, and whether the epithelial forms are the same as the lymphoid forms. These questions will be answered by completion of the murine cDNA cloning and analysis, by cDNA cloning and analysis of human pp35 and pp32, and by polymerase chain reaction amplification and analysis of cDNA from normal and neoplastic human lymphoid and epithelial tissues. These studies will clarify the interesting but presently complex picture of pp35 and pp32 expression in normal and neoplastic tissues, and will develop important reagents for use in future functional and diagnostic studies. For example, the resultant cDNA's and sequences will lead to specific hybridization and anti-peptide antibody reagents for use in studies correlating prognosis with pp35 and pp32 expression. Similarly, cloned cDNA will lead to functional studies of mutant proteins in trans- fected cells. Thus, this characterization of newly-described nuclear phosphoproteins will yield important information and will spawn a combined basic and clinical approach to the eventual understanding of their role in malignancy.
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