zo-2 gene alternative promoters in normal and neoplastic human pancreatic duct cells - Archive ouverte HAL Access content directly
Journal Articles International Journal of Cancer Year : 1999

zo-2 gene alternative promoters in normal and neoplastic human pancreatic duct cells

Abstract

We have observed that 2 forms of zonula occludens 2 (ZO-2) protein, ZO-2A and ZO-2C, are expressed in normal human pancreatic duct cells, but only ZO-2C in pancreatic duct adenocarcinoma. We report here partial organization of the zo-2 gene. Transcription of 2 forms of ZO-2 mRNA is driven by alternative promoters P(A) and P(C). Lack of expression of ZO-2A in neoplastic cells is caused by inactivation of the downstream promoter P(A). Analysis of the promoter P(A) sequence and function in normal and neoplastic cells demonstrated that neither structural changes (mutations) nor a change in the pool of transcription factors is responsible for its inactivation. Although hypermethylation was found in a large number of cancer clones, treatment with 5-aza-2'-deoxycytidine did not fully cause the promoter function to recover. We conclude that the initial down-regulation of zo-2 promoter P(A) activity in pancreatic duct carcinomas is due to the structural or functional alteration(s) in the regulatory elements, localized outside the analyzed promoter region. Methylation of P(A) is responsible for the inactivation of the suppressed promoter at the late stages of tumor development.

Dates and versions

hal-04056991 , version 1 (03-04-2023)

Identifiers

Cite

Alexandre Chlenski, Kathleen Ketels, J. Luke Engeriser, Mark Talamonti, Ming-Sound Tsao, et al.. zo-2 gene alternative promoters in normal and neoplastic human pancreatic duct cells. International Journal of Cancer, 1999, 83 (3), pp.349-358. ⟨10.1002/(sici)1097-0215(19991029)83:3<349::aid-ijc10>3.0.co;2-c⟩. ⟨hal-04056991⟩
6 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More