Expression of the obesity hormone leptin and its receptor correlates with hypoxia-inducible factor-1 alpha in human colorectal cancer.
BACKGROUND
The obesity hormone, leptin, has been found to play a role in development and proliferation of normal and malignant tissues. Leptin activity is mediated through the leptin receptor (ObR) that is often expressed in different human cancer cells. Previously, we found that the expression of leptin and ObR can be stimulated by hypoxia-mimetic agents. The aim of this study was to analyze the abundance of and relationships among leptin, ObR and hypoxia-inducible factor-1alpha (HIF-1alpha, transcriptional regulator) in human colorectal cancer.


METHODS
We investigated the expression of leptin, ObR and HIF-1alpha in colorectal cancer specimens from 135 patients who underwent curative resection.


RESULTS
Immunoreactivity for leptin, ObR and HIF-1alpha protein was observed in 69 of 135 (51.1%), 129 of 135 (95.5%) and 88 of 135 (65.2%) of colorectal cancers, respectively. Statistically significant positive correlations were noted between leptin and HIF-1alpha (P = 0.005, r = 0.243), ObR and HIF-1alpha (P < 0.001, r = 0.325) as well as leptin and ObR (P < 0.001, r = 0.426) in the group of all patients as well as in various subgroups depending on clinicopathological features.


CONCLUSIONS
The results indicate that the leptin system is overexpressed in human colorectal cancer and this overexpression appears to be associated with the abundance of HIF-1alpha.
Koda
M
M
Department of Pathomorphology, Medical University of Bialystok, Bialystok, Poland.
Sulkowska
M
M
Kanczuga-Koda
L
L
Cascio
S
S
Colucci
G
G
Russo
A
A
Surmacz
E
E
Sulkowski
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000601:surgery; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism* / Q000502:physiology; D020738:Leptin / Q000096:biosynthesis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics*; D054411:Receptors, Leptin; D015854:Up-Regulation / Q000235:genetics
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C515448:LEPR protein, human; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin