Autocrine/paracrine involvement of insulin-like growth factor-I and its receptor in chronic lymphocytic leukaemia

Chronic lymphocytic leukaemia (CLL) is characterized by the accumulation of long-lived B lymphocytes blocked in G0/1 by impaired apoptosis. As insulin-like growth factor-I (IGF-I) is known for its antiapoptotic effects in different cell types, we investigated whether IGF-I and its receptor (IGF-IR)...

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Detalles Bibliográficos
Autores principales: Schillaci, R., Galeano, A., Becu-Villalobos, D., Spinelli, O., Sapia, S., Bezares, R.F.
Formato: JOUR
Materias:
B cells
Chronic lymphocytic leukaemia (CLL)
CLL apoptosis
CLL growth factors
growth hormone
messenger RNA
protein bcl 2
somatomedin C
somatomedin C receptor
adult
aged
apoptosis
article
autocrine effect
B lymphocyte
cell cycle
cell survival
chronic lymphatic leukemia
clinical article
controlled study
female
flow cytometry
human
human cell
immunophenotyping
male
paracrine signaling
priority journal
protein expression
reverse transcription polymerase chain reaction
statistical analysis
Aged
Aged, 80 and over
Analysis of Variance
Apoptosis
Autocrine Communication
B-Lymphocytes
Case-Control Studies
Culture Media, Conditioned
Female
Flow Cytometry
Growth Hormone
Humans
Insulin-Like Growth Factor I
Leukemia, Lymphocytic, Chronic
Male
Middle Aged
Paracrine Communication
Receptor, IGF Type 1
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger
Tumor Cells, Cultured
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_00071048_v130_n1_p58_Schillaci
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario:Chronic lymphocytic leukaemia (CLL) is characterized by the accumulation of long-lived B lymphocytes blocked in G0/1 by impaired apoptosis. As insulin-like growth factor-I (IGF-I) is known for its antiapoptotic effects in different cell types, we investigated whether IGF-I and its receptor (IGF-IR) participate in autocrine/paracrine loops affecting the survival of CLL cells. IGF-IR protein and mRNA was present in CLL cells in 44% and 59% of patients respectively. IGF-IR expression in CLL patients was positively correlated with the expression of the antiapoptotic protein Bcl-2 and was involved in CLL cell survival in vitro. Serum IGF-I was elevated in CLL patients, but growth hormone (GH) was normal. CLL cells expressed IGF-I mRNA and secreted the growth factor in vitro. Therefore, local production of IGF-I can account for the increased levels of serum IGF-I, independently of GH, and may be related to autocrine/paracrine control of lymphocyte survival acting at IGF-IR. This is the first demonstration of IGF-IR expression in a subgroup of CLL patients and of its antiapoptotic effects in vitro, highlighting the importance of this growth factor receptor as a possible therapeutic target in CLL. © 2005 Blackwell Publishing Ltd.

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