Deregulated expression of prostate apoptosis response gene-4 in less differentiated lymphocytes and inverse expressional patterns of par-4 and bcl-2 in acute lymphocytic leukemia.
BACKGROUND
Prostate apoptosis response gene-4, known as par-4, is a new proapoptotic factor functionally required but not sufficient for apoptosis. Since there is evidence from prostate cancer cells that par-4 is involved in regulation of bcl-2 we assessed expression of par-4 and bcl-2 in different populations of normal and neoplastic lymphocytes.


METHODS
Expression of par-4 mRNA and protein in different subpopulations of normal and neoplastic lymphocytes was assessed by reverse transcription polymerase chain reaction and Western blot.


RESULTS
Par-4 mRNA was not detectable in lymphocytes of healthy volunteers (n = 10), but was present in the majority of samples of chronic lymphocytic leukemia (n = 30), chronic lymphocytic leukemia/prolymphocytic leukemia (n = 6) and acute lymphocytic leukemia (n = 10). Par-4 protein was expressed unanimously in samples of mononuclear cells from healthy volunteers and patients with CLL, but less frequently in immature lymphocytes, including neoplastic cells of CLL/PLL and ALL. The decreased frequency of par-4 expression in immature subpopulations was confirmed by results on lymphocytic cell lines at various stages of maturation. Comparing the expressional patterns of par-4 and bcl-2 there was an inverse relationship of both proteins in ALL and different lymphocytic cell lines, indicating a functional relationship of par-4 and bcl-2.


CONCLUSIONS
This study establishes par-4 as a factor expressed in the majority of normal and neoplastic lymphocytic cells, demonstrating a decreased frequency of protein expression in less differentiated lymphocytes and an inverse expressional pattern of par-4 and bcl-2 in lymphocytic cell lines and ALL.
Boehrer
S
S
Department of Medicine III, Johann Wolfgang Goethe-University Hospital, Frankfurt am Main, Germany.
Chow
K U
KU
Puccetti
E
E
Ruthardt
M
M
Godzisard
S
S
Krapohl
A
A
Schneider
B
B
Hoelzer
D
D
Mitrou
P S
PS
Rangnekar
V M
VM
Weidmann
E
E
D051017:Apoptosis Regulatory Proteins; D002454:Cell Differentiation; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D019169:Jurkat Cells; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism* / Q000473:pathology; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*
D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C101296:prostate apoptosis response-4 protein