Cells heterozygous for the ApcMin mutation have decreased gap junctional intercellular communication and connexin43 level, and reduced microtubule polymerization

T. Husøy, V. Cruciani, H.K. Knutsen, S.-O. Mikalsen, H.B. Ølstørn, J. Alexander

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Mutations in the tumour suppressor gene adenomatous polyposis coli ( Apc ) are early and critical events in the development of colon cancer. In the absence of functional Apc, β-catenin is not degraded in the cytoplasm and can be transported to the nucleus and turn on transcription of several genes, including the gap junction protein connexin43. Apc also stabilizes microtubules and regulates microtubule polymerization. Changes in Wnt signalling and microtubule function are reported to affect the connexin level. To study the effect of heterozygous Apc mutation we examined gap junctional intercellular communication (GJIC) in IMCE (Immorto-Min colonic epithelium) cells with one mutated Apc allele and in YAMC (Young adult mouse colon) cells with normal Apc function. IMCE cells had only half the GJIC level compared with YAMC cells. RT–PCR showed that both YAMC and IMCE cells express a common complement of seven connexin genes ( Cx26 , Cx31 , Cx39 , Cx40 , Cx43 , Cx45 and Cx50 ), with an additional Cx29 gene expression in YAMC cells. We found that the Cx43 level was correspondingly lower in IMCE cells as detected by western blotting and immunofluorescence. There were no differences in the level or localization of β-catenin and the downstream gene E-cadherin between the cells, indicating no activation of the Wnt-signalling pathway in cells with one mutated Apc allele. We also examined the microtubule polymerization rate, and IMCE cells had markedly slower microtubule polymerization than YAMC cells. Hence, it appears that mutation in one Apc allele is sufficient to affect microtubule function, while inactivation of both wild-type Apc alleles may be necessary for activation of Wnt signalling. Reduction in GJIC and Cx43 level in IMCE cells may be caused by reduced Cx43 transport as a result of alterations in microtubule function.
Original languageEnglish
Pages (from-to)643-650
Number of pages8
JournalCarcinogenesis
Volume24
Issue number4
DOIs
Publication statusPublished - 2003

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