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Updated: Jun 21, 2026
Chromosome Preparation From Cultured Cells
Published on: January 28, 2014
Chromosome 14 transfer and functional studies identify a candidate tumor suppressor gene, mirror image polydactyly 1,
Arthur Kwok Leung Cheung1, Hong Lok Lung, Josephine Mun Yee Ko
1Department of Biology and Center for Cancer Research, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, People's Republic of China.
Abstract:
Chromosome 14 allelic loss is common in nasopharyngeal carcinoma (NPC) and may reflect essential tumor suppressor gene loss in tumorigenesis. An intact chromosome 14 was transferred to an NPC cell line using a microcell-mediated chromosome transfer approach. Microcell hybrids (MCHs) containing intact exogenously transferred chromosome 14 were tumor suppressive in athymic mice, demonstrating that intact chromosome 14 NPC MCHs are able to suppress tumor growth in mice. Comparative analysis of these MCHs and their derived tumor segregants identified 4 commonly eliminated tumor-suppressive CRs. Here we provide functional evidence that a gene, Mirror-Image POLydactyly 1 (MIPOL1), which maps within a single 14q13.1-13.3 CR and that hitherto has been reported to be associated only with a developmental disorder, specifically suppresses in vivo tumor formation. MIPOL1 gene expression is down-regulated in all NPC cell lines and in approximately 63% of NPC tumors via promoter hypermethylation and allelic loss. SLC25A21 and FOXA1, 2 neighboring genes mapping to this region, did not show this frequent down-regulated gene expression or promoter hypermethylation, precluding possible global methylation effects and providing further evidence that MIPOL1 plays a unique role in NPC. The protein localizes mainly to the nucleus. Re-expression of MIPOL1 in the stable transfectants induces cell cycle arrest. MIPOL1 tumor suppression is related to up-regulation of the p21(WAF1/CIP1) and p27(KIP1) protein pathways. This study provides compelling evidence that chromosome 14 harbors tumor suppressor genes associated with NPC and that a candidate gene, MIPOL1, is associated with tumor development.
Insights
Loss of chromosome 14 in nasopharyngeal carcinoma (NPC) suggests tumor suppressor gene loss. Transferring chromosome 14 suppressed NPC tumor growth, identifying MIPOL1 as a key tumor suppressor gene.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Allelic loss on chromosome 14 is frequent in nasopharyngeal carcinoma (NPC), indicating potential loss of critical tumor suppressor genes.
- Tumorigenesis in NPC may involve the inactivation of genes located on chromosome 14.
Purpose of the Study:
- To investigate the tumor suppressive capacity of chromosome 14 in nasopharyngeal carcinoma.
- To identify specific genes on chromosome 14 that contribute to tumor suppression in NPC.
Main Methods:
- Microcell-mediated chromosome transfer was used to introduce an intact chromosome 14 into NPC cell lines.
- Comparative analysis of microcell hybrids (MCHs) and derived tumors identified candidate tumor suppressor regions (CRs).
- Functional studies were performed on the identified gene, Mirror-Image POLydactyly 1 (MIPOL1).
Main Results:
- Exogenous chromosome 14 transfer suppressed NPC tumor growth in vivo.
- Four CRs were identified as commonly eliminated in tumors, with MIPOL1 mapping to a specific 14q13.1-13.3 CR.
- MIPOL1 expression was down-regulated in NPC cell lines and tumors due to promoter hypermethylation and allelic loss.
- MIPOL1 re-expression induced cell cycle arrest and suppressed tumor formation by up-regulating p21(WAF1/CIP1) and p27(KIP1) pathways.
Conclusions:
- Chromosome 14 harbors crucial tumor suppressor genes involved in nasopharyngeal carcinoma development.
- MIPOL1 is a novel tumor suppressor gene in NPC, functionally inhibiting tumor formation through cell cycle regulation.
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