Molecular and Cellular Biochemistry

, Volume 297, Issue 1–2, pp 179–187 | Cite as

A novel loss-of-function mutation in TP53 in an endometrial cancer cell line and uterine papillary serous carcinoma model

  • Zhihe Liu
  • Guanghua Wan
  • Christopher Heaphy
  • Marco Bisoffi
  • Jeffrey K. Griffith
  • Chien-an A. Hu


The etiology of carcinoma of the uterine endometrium (ECa) is poorly understood. However, loss of apoptosis is one of the major factors that allow cancer cells to survive and progress. Hec50co, a poorly differentiated human ECa cell line, is widely used in the investigation of ECa. Previously, Hec50co xenograft tumor model in nude mice developed an advanced phenotype, similar to that of uterine papillary serous carcinoma (UPSC). Importantly, loss-of-function mutation in tumor suppressor TP53 was found in 20–30% of all ECa and >90% of UPSC. Thus, understanding the status of TP53 in Hec50co is essential for using Heco50co as a model for UPSC. To obtain an accurate genotype–phenotype status of TP53 in Hec50co, we performed mutation and functional analysis of TP53 gene of Hec50co by RT-PCR, genomic-PCR, and cloning and expression of mutant and wildtype TP53 alleles. We found a novel 42-bp deletion mutation in the exon6–intron6 splice junction of TP53 (TP53.del42bp) leading to a 113-bp exon6-deleted/skipped transcript was identified in Hec50co. In addition, the other TP53 allele in Hec50co is inactivated through a large deletion. Adenovirus (AD) harboring wildtype full-length TP53 cDNA induces caspase-dependent apoptosis; while the AD-TP53.del42bp allele does not. In addition, messenger RNA of TP53.del42bp allele is stable whereas the protein product of TP53.del42bp allele is made but not stable. Taken together, we demonstrate that Hec50co is a TP53-null cell line possessing one TP53.del42bp allele and the other lost allele and therefore provides an excellent model to dissect the molecular and cellular bases of UPSC and other p53-null cancers.


TP53 loss-of-function splicing mutation loss of heterozygosity allelic loss endometrial cancer Hec50co adenovirus TP53-null cancer 


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The authors would like to thank Drs. D. Dai and K. Leslie for providing the Hec50co cell line. This work is supported by NM-INBRE grant (2 P20 RR016480-04) and NCI-RO1 (1 RO1 CA106644-01) [to C.-A. A. H.].


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Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • Zhihe Liu
    • 1
  • Guanghua Wan
    • 1
  • Christopher Heaphy
    • 1
  • Marco Bisoffi
    • 1
  • Jeffrey K. Griffith
    • 1
  • Chien-an A. Hu
    • 1
  1. 1.Department of Biochemistry and Molecular BiologyUniversity of New Mexico School of MedicineAlbuquerqueUSA

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