Alterations in the expression of α6β4 integrin and p21/WAF1/Cip1 in N-nitrosomethylbenzylamine–induced rat esophageal tumorigenesis

✍ Scribed by Leena Khare; Carol L. K. Sabourin; Barry R. DeYoung; Beth A. Wagner; Gary D. Stoner

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Volume: 21
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/(sici)1098-2744(199803)21:3<185::aid-mc6>3.0.co;2-l

✦ Synopsis

Integrin α6β4 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 Nnitrosomethylbenzylamine (NMBA), α6 and β4 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 β4 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 α6A, α6B, and β4 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 β4 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 α6β4 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. β4 expression was significantly reduced and α6A expression was decreased and delocalized in papillomas. These findings suggest that alteration in α6β4 integrin and p21/WAF1/Cip1 expression may be an important biomarker for tumor progression in NMBAinduced rat esophageal tumorigenesis.