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.