pp32 reduction induces differentiation of TSU-Pr1 cells.
pp32 (ANP32A) is a nuclear phosphoprotein expressed as a nonmutated form in self-renewing cell populations and neoplastic cells. Mechanistically, pp32 may regulate pathways important in the process of differentiation as part of separate complexes inhibiting histone acetylation and regulating immediate-early and cytokine mRNA stability. Prostatic adenocarcinomas express pp32 in a differentiation related manner-well-differentiated tumors express lower levels of pp32 than poorly differentiated tumors. In benign prostate, pp32 is expressed in basal cells but not in terminally differentiated glandular cells. Based on these observations, we hypothesized that reduction of pp32 expression might be an important differentiation signal. We used anti-sense pp32 and RNAi transfection to study the effects of reduced pp32 expression in the TSU-Pr1 carcinoma cell line. pp32 reduction induced TSU-Pr1 cells to differentiate into neuronal-like cells with associated inhibition of growth. Reduction of pp32 and consequent differentiation were accompanied by a marked reduction in expression of SET, which complexes with pp32, by a marked change in acetylation status of histone H4, and by further differential expression of genes in differentiation pathways. Thus, reduction of pp32 in the undifferentiated TSU-Pr1 neoplastic cell line induces differentiation and thus may be an element of a differentiation control pathway in both normal and neoplastic cells.
Brody
Jonathan R
JR
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Kadkol
Shrihari S
SS
Hauer
M Claire
MC
Rajaii
Fatemeh
F
Lee
Jessica
J
Pasternack
Gary R
GR
D000107:Acetylation; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D045744:Cell Line, Tumor; D002868:Chromosomal Proteins, Non-Histone; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D056488:Histone Chaperones; D006657:Histones / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D014162:Transfection
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; D006657:Histones; D015850:Interleukin-6; D009687:Nuclear Proteins; D010750:Phosphoproteins; D018809:Proliferating Cell Nuclear Antigen; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C513473:SET protein, human; D014157:Transcription Factors; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases