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Expression patterns of PHF5A/Phf5a and GJa1/Gja1 in rat and human endometrial cancer
University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
2013 (English)In: Cancer Cell International, ISSN 1475-2867, Vol. 13, no 1, 43Article in journal (Refereed) Published
Abstract [en]

Endometrial adenocarcinoma is the most frequently diagnosed cancer of the female genital tract in the western world. Studies of complex diseases can be difficult to perform on human tumor samples due to the high genetic heterogeneity in human. The use of rat models is preferable since rat has similarities in pathogenesis and histopathological properties to that of human.

A genomic region including the highly conserved Phf5a gene associated to development of EAC has previously been identified in an association study. PHF5A has been suggested to acts as a transcription factor or cofactor in the up regulation of expression of Gja1 gene in the presence of estrogen. It has earlier been shown that the Phf5a gene is down regulated in rat EAC derived cell lines by means of expression microarrays.

We analyzed the expression of Phf5a and Gja1 by qPCR, and potential relations between the two genes in EAC tumors and non-malignant cell lines derived from the BDII rat model. In addition, the expression pattern of these genes was compared in rat and human EAC tumor samples.

Changes in expression for Phf5a/PHF5A were found in tumors from both rat and human even though the observed pattern was not completely consistent between the two species. By separating rat EAC cell lines according to the genetic background, a significant lower expression of Phf5a in one of the two cross backgrounds was revealed, but not for the other. In contrast to other studies, Phf5a/PHF5A regulation of Gja1/GJA1 was not revealed in this study.

Place, publisher, year, edition, pages
BioMed Central, 2013. Vol. 13, no 1, 43
Keyword [en]
BDII, Endometrial cancer, Genetic background, Phf5a, Gja1
National Category
Medical and Health Sciences
Research subject
Medical sciences
Identifiers
URN: urn:nbn:se:his:diva-7420DOI: 10.1186/1475-2867-13-43ISI: 000319389700001PubMedID: 23675859Scopus ID: 2-s2.0-84878075429OAI: oai:DiVA.org:his-7420DiVA: diva2:611671
Available from: 2013-03-18 Created: 2013-03-18 Last updated: 2015-08-13Bibliographically approved
In thesis
1. Genomic and genetic alterations in endometrial adenocarcinoma
Open this publication in new window or tab >>Genomic and genetic alterations in endometrial adenocarcinoma
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The most frequently diagnosed cancer of the female genital tract is cancer of the endometrium (endometrial cancer), ranking fourth among the invasive tumors that affect women in Europe and North America. As most other cancer types, endometrial cancer is a complex genetic disease influenced by both genetic and environmental factors.

The human population is genetically heterogeneous and studies of complex diseases in human are proven to be difficult. By using a model system such as the BDII rat, some of the obstacles related to the study of complex diseases can be avoided. The BDII rat strain is prone to spontaneously develop endometrial adenocarcinoma (EAC) and more than 90% of the virgin females develop EAC during their lifetime. Development of EAC tumors in BDII rats is comparable in pathogenesis and histopathological properties to that of human.

The aims of this thesis were i/ to characterize EAC in the BDII rat experimental model system by analyzing structural and numerical chromosome aberrations, ii/ to evaluate the importance of the genetic set-up in EAC development, and iii/ to determine the impact of genomic and genetic alterations on the functionality of candidate genes in rat EAC and in human endometrial tumors of different FIGO grades.

Non-random numerical and structural aberrations that could contribute to tumor formation were identified, and evidence that the genetic background had a significant influence on the genome make-up of tumor cells was provided. Certain genes (Gpx3/GPX3, Met/MET, Phf5a/PHF5A, and Gja1/GJA1) were selected for further analysis and aberrant expression of some of them were found in both rat and human EACs. By separating EAC cell lines according to the genetic cross background, for two of the genes (Phf5 and Met), we showed that the expression pattern differed significantly between different cross backgrounds, which clearly pinpoint the importance of using animal models as a complement to clinical studies in identification of cancer-related genes.

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2013
Keyword
Endometrial cancer, Genetic background, BDII rat model, SKY, Chromosomal abreations, Gene expression
National Category
Natural Sciences
Research subject
Natural sciences
Identifiers
urn:nbn:se:his:diva-7421 (URN)978-91-7668-913-4 (ISBN)
Public defence
2013-03-01, Insikten, Högskolan i Skövde, Skövde, 13:15 (Swedish)
Opponent
Supervisors
Available from: 2013-03-18 Created: 2013-03-18 Last updated: 2014-03-27Bibliographically approved

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