Enhancement of erbB2 and erbB3 expression during oral oncogenesis in diabetic rats.
OBJECTIVE
The expression of erbB2 and erbB3 receptors was investigated in an experimental model of chemically induced oral carcinogenesis in normal and diabetic (type I) Sprague-Dawley rats.


METHODS
Thirteen diabetic and twelve normal rats developed precancerous and cancerous lesions after 4-nitroquinoline-N-oxide treatment, while six diabetic and six normal animals were used as controls. Sections of biopsies from all animals were classified histologically in the following categories: normal mucosa, hyperplasia, dysplasia, early invasion, well- and moderately-differentiated squamous cell carcinoma. Each section was studied immunohistochemically using monoclonal antibodies against erbB2 and erbB3 proteins and six representative histological regions in each section were analysed.


RESULTS
The erbB2 was expressed at very low levels in normal rats, while in diabetic animals its expression was significantly increased during early invasion (P = 0.04). The erbB3 expression was significantly elevated in well-differentiated carcinoma in normal animals (P = 0.01), while in diabetic animals it was significantly increased during oral mucosal hyperplasia and dysplasia (P = 0.03 and 0.0007, respectively). The comparison of erbB2 expression between diabetic and normal rats revealed significant differences in all stages except for the tumor stage of moderately differentiated carcinoma (P = 0.01, 0.00001, 0.00001, 0.003, and 0.00001). In regard to erbB3 expression, significant differences between diabetic and normal rats existed only in normal, non-cancerous and precancerous stages (P = 0.007, 0.0001, 0.0003).


CONCLUSIONS
It seems that diabetes enhances the expression of both erbB2 and erbB3 in certain stages of oral oncogenesis possibly resulting in promotion of cell proliferation and inhibition of apoptosis.
Vairaktaris
Eleftherios
E
Department of Oral and Maxillofacial Surgery, University of Athens Medical School, Vas. Sofias 93 and Dim. Soutsou 1, Athens 11521, Greece. lvairakt@med.uoa.gr
Goutzanis
Lambros
L
Vassiliou
Stavros
S
Spyridonidou
Sofia
S
Nkenke
Emeka
E
Papageorgiou
Georgios
G
Strantzias
Pashalis
P
Lazaris
Andreas
A
Yapijakis
Christos
C
Patsouris
Efstratios
E
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D048909:Diabetes Complications / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004195:Disease Models, Animal; D005260:Female; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D020893:Receptor, ErbB-3 / Q000378:metabolism*
D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3
J Surg Oncol. 2003 Jan;82(1):34-50
12501167
Eur Arch Otorhinolaryngol. 1993;250(7):392-5
8286103
EMBO J. 1987 Mar;6(3):605-10
3034598
Oncology. 1998 Mar-Apr;55(2):161-7
9499191
Am J Surg. 1996 Dec;172(6):681-3
8988677
Exp Cell Res. 2003 Mar 10;284(1):89-98
12648468
J Biol Chem. 2001 Jun 15;276(24):21544-54
11278889
J Biol Chem. 1994 May 20;269(20):14661-5
7514177
Oral Oncol. 2007 Feb;43(2):165-73
16860589
Mol Cell Biol. 1994 Jun;14(6):3550-8
7515147
Biochem J. 1994 Nov 15;304 ( Pt 1):17-21
7998930
Endocrinology. 1997 Dec;138(12):5195-201
9389501
Int J Oral Maxillofac Surg. 1998 Jun;27(3):209-12
9662015
Cancer Lett. 2002 Dec 5;186(2):137-50
12213283
J Contemp Dent Pract. 2005 Nov 15;6(4):1-16
16299602
Cancer Lett. 2002 Oct 28;184(2):215-22
12127694
Med Oral. 2003 Nov-Dec;8(5):374-81
14595263
Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4640-5
11287630
Oral Oncol. 2000 Jan;36(1):100-5
10889928
EMBO J. 1996 May 15;15(10):2452-67
8665853
Cancer Lett. 1995 Aug 16;95(1-2):79-83
7656248
Anticancer Res. 2001 May-Jun;21(3B):1953-63
11497283
Jpn J Cancer Res. 1990 May;81(5):489-94
1974247
Diabetes Care. 2004 Mar;27(3):770-4
14988300
J Pathol. 2001 Oct;195(3):343-8
11673832
Clin Cancer Res. 1995 Nov;1(11):1413-20
9815939
Cancer Lett. 2002 Oct 28;184(2):223-30
12127695
J Biol Chem. 2003 May 2;278(18):15641-51
12594228
Gynecol Oncol. 1992 Nov;47(2):179-85
1361478
Cancer Lett. 1992 Aug 31;65(3):215-20
1355405
EMBO J. 1992 Sep;11(9):3469-79
1380456
Orv Hetil. 2002 Dec 8;143(49):2731-3
12587541
J Pathol. 1993 Jul;170(3):271-8
8133400
Exp Cell Res. 2003 Mar 10;284(1):54-65
12648465
Cancer Res. 1990 Jul 1;50(13):4087-91
1972347
J Clin Invest. 1993 Oct;92(4):1787-94
7691886
Postgrad Med. 1997 Dec;102(6):117-26
9406568
Anticancer Res. 2002 Sep-Oct;22(5):3061-5
12530043
Oral Oncol. 2006 May;42(5):540-50
16464633
Bioessays. 1993 Dec;15(12):815-24
7908191
Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9660-4
9275179
Science. 1985 Sep 6;229(4717):974-6
2992089
Int J Exp Pathol. 2003 Dec;84(6):259-65
14748745
J Biol Chem. 2002 Mar 15;277(11):8961-9
11779863
Aust Dent J. 1998 Oct;43(5):315-20
9848981
Clin Cancer Res. 1999 Dec;5(12):4164-74
10632356