Autocrine regulation of human prostate carcinoma cell proliferation by somatostatin through the modulation of the SH2 domain containing protein tyrosine phosphatase (SHP)-1.
The present study was intended to gain additional information on the growth regulation of prostate by somatostatin (SRIF) and the intracellular events involved. The human prostate adenocarcinoma cell lines PC-3 and LNCaP produce SRIF and express subtypes 2 and 5 of SRIF receptors. The secretion of SRIF is related to the proliferative status of these cells; an inverse relationship exists between cell proliferation and the amount of secreted SRIF. Moreover, the growth of PC-3 cells is inhibited by SRIF overexpression and increased by blockage of endogenous SRIF. Coincident with the increase in SRIF secretion, the activity and levels of the SH2 domain containing protein tyrosine phosphatase (SHP)-1, present in PC-3 cells are augmented, but the effect can be partially prevented by neutralization of secreted endogenously SRIF. The activity of SHP-1 is also stimulated by the SRIF analog RC160. Overexpression of SHP-1 induces inhibition of PC-3 cell growth. SHP-1 is also present in normal prostate, benign prostatic hyperplasia, prostatic intraepithelial neoplasia, and well differentiated adenocarcinoma. In contrast, no signal is detected in poorly differentiated prostate cancer. These findings demonstrate that SRIF inhibits PC-3 and LNCaP cell proliferation through an autocrine/paracrine SRIF loop. This effect could be mediated by activation of the tyrosine phosphatase SHP-1 detected in these cells as well as in human prostate and prostate cancer.
Zapata
Pedro Darío
PD
Departamento de Bioquímica y Biología Molecular, Universidad de Alcalá, Alcalá de Henares-Madrid E-28871, Spain.
Ropero
Rosa María
RM
Valencia
Ana Montserrat
AM
Buscail
Louis
L
López
Jose Ignacio
JI
Martín-Orozco
Rosa María
RM
Prieto
Juan Carlos
JC
Angulo
Javier
J
Susini
Christiane
C
López-Ruiz
Pilar
P
Colás
Begoña
B
D019898:Autocrine Communication / Q000502:physiology*; D002277:Carcinoma / Q000473:pathology*; D002455:Cell Division / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D011467:Prostate / Q000201:enzymology; D011471:Prostatic Neoplasms / Q000473:pathology*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000502:physiology*; D017481:Receptors, Somatostatin / Q000378:metabolism; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D013004:Somatostatin / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured; D018909:src Homology Domains / Q000502:physiology*
D047908:Intracellular Signaling Peptides and Proteins; D017481:Receptors, Somatostatin; D013004:Somatostatin; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases