Alterations in the expression of alpha6beta4 integrin and p21/WAF1/Cip1 in N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis. Mol Carcinog 1998 Mar;21(3):185-93
Date
04/16/1998Pubmed ID
9537650Scopus ID
2-s2.0-0031594820 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
Integrin alpha6beta4 is altered in many neoplastic cells, but no data exist to show this happens in esophageal neoplasms. To examine the expression of this integrin in rat esophageal tumorigenesis induced by N-nitrosomethylbenzylamine (NMBA), (alpha6 and beta4 expression was evaluated in normal esophageal epithelium, in NMBA-induced preneoplastic lesions, and in papillomas by quantitative reverse transcription (RT)-polymerase chain reaction (PCR) and immunohistochemical analysis. Because the 34 subunit of this integrin has been found to cause cell-cycle arrest by the induction of p21/WAF1/Cip1, the expression of p21/WAF1/Cip1 was also analyzed by RT-PCR. Compared with the levels in normal epithelium, the alpha6A, alpha6B, and beta4 integrin levels in esophageal papillomas were 1.9-, 2.2-, and 2.1-fold lower, respectively. RT-PCR analysis showed no significant differences in integrin levels between preneoplastic and normal samples, and northern blot analysis of the beta4 integrin produced results in agreement with the RT-PCR results. The p21/WAF1/Cip1 level was decreased 1.6-fold in preneoplastic tissues and 3.1-fold in papilloma samples when compared with the mRNA levels in normal epithelium. Immunostaining showed that alpha6beta4 integrin was localized at the basolateral surface of the basal cells in normal esophageal epithelium. In preneoplastic lesions, however, the expression of this integrin was not polarized and was expressed in basal cells as well as in suprabasal cells. Beta4 expression was significantly reduced and alpha6A expression was decreased and delocalized in papillomas. These findings suggest that alteration in alpha6beta4 integrin and p21/WAF1/Cip1 expression may be an important biomarker for tumor progression in NMBA-induced rat esophageal tumorigenesis.
Author List
Khare L, Sabourin CL, DeYoung BR, Wagner BA, Stoner GDMESH terms used to index this publication - Major topics in bold
AnimalsAntigens, Surface
Biomarkers, Tumor
Blotting, Northern
Carcinogens
Cyclin-Dependent Kinase Inhibitor p21
Cyclins
Dimethylnitrosamine
Disease Models, Animal
Disease Progression
Esophageal Neoplasms
Esophagus
Fluorescent Antibody Technique
Integrin alpha6beta4
Integrins
Male
Polymerase Chain Reaction
Precancerous Conditions
RNA, Messenger
Rats
Rats, Inbred F344
Transcription, Genetic
