Glucose-dependent insulinotropic polypeptide stimulates the proliferation of colorectal cancer cells.
Although numerous epidemiological studies have provided convincing evidence for an increase in the prevalence of colorectal cancer (CRC) in obese individuals, the precise mechanisms involved have not been elucidated. Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal regulatory peptide whose primary physiologic role is to stimulate postprandial pancreatic insulin secretion. Like insulin, GIP has been linked to enhanced nutrient efficiency, which occurred during the course of evolution. Its expression is increased in obesity, and we thus initiated studies to examine whether GIP might contribute to the pathogenesis of obesity-related CRC. RT-PCR and Western analysis demonstrated the presence of the GIP receptor (GIPR) in several human CRC cell lines. GIP stimulated the proliferation of MC-26 cells, a mouse CRC cell line, in a concentration-dependent manner. Western analysis showed that GIP induced the activity of several downstream signaling molecules known to be involved in cellular proliferation in a concentration- and time-dependent manner. These studies indicate that the presence of GIP receptors in CRC may enable ligand binding and, in so doing, stimulate CRC cell proliferation. The overexpression of GIP, which occurs in obesity, might thereby be contributing to the enhanced rate of carcinogenesis observed in obesity.
Prabakaran
Daniel
D
Department of Medicine, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts 02118, United States.
Wang
Baogui
B
Feuerstein
Joseph D
JD
Sinclair
Jennifer A
JA
Bijpuria
Priti
P
Jepeal
Lisa I
LI
Wolfe
M Michael
MM
D000818:Animals; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000473:pathology*; D005749:Gastric Inhibitory Polypeptide / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D051379:Mice; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism; D013552:Swine
D008024:Ligands; D011964:Receptors, Gastrointestinal Hormone; D005749:Gastric Inhibitory Polypeptide; C041086:gastric inhibitory polypeptide receptor