CCK2 gastrin receptor as a potential target for therapy in leukaemia cell lines.
The gastrin CCK2 pathway has been implicated in the development of various cancers including leukaemia. An autocrine or intracrine pathway may exist in the leukaemia cell that is involved in stimulating proliferation. We tested four leukaemia cell lines, KU812, ML-1, MOLT-4 and U937 for the existence of the CCK2 receptor and gastrin precursor protein using immunoblotting. We also assessed the effect of CCK2 antagonist PD 135 and both gastrin 17 and glycine-extended gastrin on the proliferation of the cell lines. We found immunoreactive CCK2 and gastrin precursors present in all 4 cell lines. We also observed a stimulatory effect on proliferation by gastrin and glycine-extended gastrin on 2 and 3 of the cell lines respectively and an inhibitory effect of PD 135 on all 4 cell lines. These results demonstrate that the gastrin-gastrin receptor axis is a potential target for new therapeutic strategies.
Stubbs
M
M
Department of Medicine, Royal Free Hospital, Pond Street, London NW3 2PF, UK.
Khan
K
K
Wickremasinghe
R G
RG
Ganeshaguru
K
K
Caplin
M E
ME
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D005755:Gastrins / Q000737:chemistry / Q000378:metabolism; D005998:Glycine / Q000737:chemistry; D006801:Humans; D015151:Immunoblotting; D007938:Leukemia / Q000628:therapy*; D011485:Protein Binding; D011498:Protein Precursors / Q000737:chemistry; D043887:Receptor, Cholecystokinin B / Q000378:metabolism / Q000502:physiology*; D011949:Receptors, Cholecystokinin / Q000378:metabolism; D020298:U937 Cells
D005755:Gastrins; D011498:Protein Precursors; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C013706:big gastrin; D005998:Glycine