Expression of connexin26 in islets of Langerhans is associated with impaired glucose tolerance in patients with pancreatic adenocarcinoma.
OBJECTIVE
Impairment of glucose tolerance is one of the leading clinical presentations in patients with pancreatic carcinoma. The mechanism of disturbed glucose metabolism, however, is still under debate. Using microarray technology, key mechanisms of deregulated molecular functions of cancer cell-specific mRNAs and tumor-induced mRNAs in peritumorous tissue should be identified in pancreatic ductal adenocarcinoma (PDAC) by comparison to chronic pancreatitis and normal pancreas.


METHODS
Forty-three mRNAs were abundant in tissue specimens of patients operated due to pancreatic carcinoma but absent or of low abundance in chronic pancreatitis and normal pancreas. One of these mRNAs encodes the gap junction protein connexin26, known as a tumor suppressor, which was 10.8- and 6.9-fold more abundant in pancreatic carcinoma than in normal pancreas and chronic pancreatitis, respectively. Quantitative RT-PCR was performed for connexin26, with mRNA being expressed 26.7- and 2.9-fold more than in normal pancreas (n = 6), in pancreatic carcinoma (n = 7), and chronic pancreatitis (n = 8), respectively.


RESULTS
By immunohistochemistry, connexin26 was predominantly localized to the islets in the vicinity of the pancreatic carcinoma tissue. Control sections of tissue with chronic pancreatitis and normal pancreas show connexin26 expression in the islets as well. Interestingly, the level of mRNA abundance (fold over normal pancreas) in RT-PCR correlates (r = 0.62) with the 2h value of the pre-operative oral glucose tolerance test of these patients.


CONCLUSIONS
Whether overexpressed connexin26 in pancreatic cancer is a cause of impaired glucose tolerance remains to be elucidated in further experimental studies.
Pfeffer
Frank
F
Department of General and Visceral Surgery, Albert-Ludwigs-University, Freiburg, Germany.
Koczan
Dirk
D
Adam
Ulrich
U
Benz
Stefan
S
von Dobschuetz
Ernst
E
Prall
Friedrich
F
Nizze
Horst
H
Thiesen
Hans-Jürgen
HJ
Hopt
Ulrich T
UT
Löbler
Marian
M
D000230:Adenocarcinoma / Q000150:complications / Q000235:genetics*; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D018149:Glucose Intolerance / Q000235:genetics*; D044882:Glucose Metabolism Disorders / Q000209:etiology / Q000235:genetics*; D006801:Humans; D007515:Islets of Langerhans / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000150:complications / Q000235:genetics*
D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26