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Human APC2 localization and allelic imbalance.

C R Jarrett¹, J Blancato, T Cao

¹The Lombardi Cancer Research Center, Georgetown University School of Medicine, Washington, DC 20007, USA.

Cancer Research

|November 3, 2001

Summary

The adenomatous polyposis coli (APC) gene APC2 is located on chromosome 19p13.3 and shows allelic imbalance in ovarian cancers, suggesting it may be a tumor suppressor gene.

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Area of Science:

Genetics
Molecular Biology
Oncology

Background:

A second adenomatous polyposis coli (APC)-like gene, APC2/APCL, has been identified and mapped to chromosome 19.
The APC2 gene is located in a chromosomal region frequently lost in various cancers, notably ovarian cancer.

Purpose of the Study:

To fine-map the APC2 gene to a specific chromosomal region.
To investigate the potential role of APC2 as a tumor suppressor gene in ovarian cancer.
To determine the subcellular localization and interactions of APC2 in ovarian cancer cells.

Main Methods:

Fine mapping of APC2 using genetic markers.
Interphase fluorescence in situ hybridization (FISH) to assess allelic imbalance in ovarian cancers.
Overexpression of APC2 in SKOV3 ovarian cancer cells and immunofluorescence microscopy to determine localization.
Treatment with cytochalasin D to assess APC2 association with actin filaments.

Main Results:

APC2 was fine-mapped to chromosome 19p13.3, encompassing markers D19S883 and WI-19632.
Nineteen out of twenty ovarian cancers screened showed APC2 allelic imbalance.
Exogenously expressed APC2 localized to the Golgi apparatus, actin structures, and microtubules in SKOV3 cells.
Endogenous APC2 colocalized with the Golgi apparatus and actin filaments, remaining associated even after actin disruption.

Conclusions:

APC2 is a potential tumor suppressor gene in ovarian cancer due to its location and allelic imbalance.
APC2 is involved in actin-associated cellular events, potentially influencing cell motility and adhesion.
APC2 may function independently or with APC to regulate beta-catenin signaling.