Differential regulation and localization of β-catenin and cell cycle regulating proteins in Barrett’s esophageal carcinoma: The possible essential signaling factors in the development of esophageal adenocarcinoma

814 With a view to investigate the role of β-catenin and some cell cycle regulatory proteins like cyclin-B1, Cdc-2, pCdc-2 and pCdc-25C, immunohistochemical localization of β-catenin, Cdc-2 and PCNA were carried out with concomitant detection of β-catenin, cyclin-B1, Cdc-2, pCdc-2 and pCdc-25C by Western blot technique in normal Barrett’s esophagus (BE), low grade dysplasia (LGD), high grade dysplasia (HGD) and esophageal adenocarcinoma (EA) samples. Immunohistochemical detection of β-catenin, Cdc2 and PCNA showed grade specific and tissue specific expressions in relation to the patterns of disease progression. In normal BE, LGD and HGD, β-catenin was mainly noted to be localized in the plasma membrane and cytoplasm; nuclear expression appeared to be insignificant. In adenocarcinoma samples the intensities of β–catenin expression in both membrane and cytoplasm appeared very insignificant. The expression of receptors of β-catenin (TCF-3) appeared almost same in all the samples in both WB and immunohistochemistry. Cdc-2 was noted to be mainly localized in the cytoplasm and is pronounced in the HGD and EA samples. PCNA exhibited tissue specific as well as grade specific expression. Western blot analyses also presented less expression of β-catenin in HGD and almost no expression in EA samples. Cyclin-B1 exhibited more or less similar expressions in all the samples except slightly less expression in LGD. pCdc-2 expression was more or less uniform in all the samples except comparatively less expression in HGD. pCdc-25C expression was relatively low in normal BE and LGD but comparatively higher expression was noted in HGD and EA samples. Less expression of β-catenin in the nucleus of different samples led us to propose its down regulation in the nucleus and alternative mode of function in inducing esophageal carcinoma, it might have indirect role in the trans-activation of different genes to potentiate cell proliferation. In conclusion, these studies suggest a possible role of β-catenin signaling network along with different cell cycle regulating factors in the sequential development of Barrett’s esophageal cancer.