Tumorigenesis and peritoneal colonization from fallopian tube epithelium

Sharon L. Eddie, Suzanne M. Quartuccio, Eoghainin Ó. hAinmhire, Georgette Moyle-Heyrman, Dan D. Lantvit, Jian-Jun Wei, Barbara C. Vanderhyden, Joanna E. Burdette

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Abstract

Ovarian cancer is the most lethal gynecological malignancy, primarily because its origin and initiation factors are unknown. A secretory murine oviductal epithelial (MOE) model was generated to address the hypothesis that the fallopian tube is an origin for high-grade serous cancer. MOE cells were stably altered to express mutation in p53, silence PTEN, activate AKT, and amplify KRAS alone and in combination, to define if this cell type gives rise to tumors and what genetic alterations are required to drive malignancy. Cell lines were characterized in vitro and allografted into mice. Silencing PTEN formed high-grade carcinoma with wide spread tumor explants including metastasis into the ovary. Addition of p53 mutation to PTEN silencing did not enhance this phenotype, whereas addition of KRAS mutation reduced survival. Interestingly, PTEN silencing and KRAS mutation originating from ovarian surface epithelium generated endometrioid carcinoma, suggesting that different cellular origins with identical genetic manipulations can give rise to distinct cancer histotypes. Defining the roles of specific signaling modifications in tumorigenesis from the fallopian tube/oviduct is essential for early detection and development of targeted therapeutics. Further, syngeneic MOE allografts provide an ideal model for pre-clinical testing in an in vivo environment with an intact immune system.

Original languageEnglish
Pages (from-to)20500-20512
Number of pages13
JournalOncotarget
Volume6
Issue number24
DOIs
Publication statusPublished - 04 May 2015

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Fallopian Tubes
Carcinogenesis
Epithelium
Neoplasms
Mutation
Endometrioid Carcinoma
Peptide Initiation Factors
Oviducts
Ovarian Neoplasms
Allografts
Ovary
Immune System
Epithelial Cells
Neoplasm Metastasis
Carcinoma
Phenotype
Cell Line

Cite this

Eddie, S. L., Quartuccio, S. M., hAinmhire, E. Ó., Moyle-Heyrman, G., Lantvit, D. D., Wei, J-J., ... Burdette, J. E. (2015). Tumorigenesis and peritoneal colonization from fallopian tube epithelium. Oncotarget, 6(24), 20500-20512. https://doi.org/10.18632/oncotarget.3985
Eddie, Sharon L. ; Quartuccio, Suzanne M. ; hAinmhire, Eoghainin Ó. ; Moyle-Heyrman, Georgette ; Lantvit, Dan D. ; Wei, Jian-Jun ; Vanderhyden, Barbara C. ; Burdette, Joanna E. / Tumorigenesis and peritoneal colonization from fallopian tube epithelium. In: Oncotarget. 2015 ; Vol. 6, No. 24. pp. 20500-20512.
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Eddie, SL, Quartuccio, SM, hAinmhire, EÓ, Moyle-Heyrman, G, Lantvit, DD, Wei, J-J, Vanderhyden, BC & Burdette, JE 2015, 'Tumorigenesis and peritoneal colonization from fallopian tube epithelium', Oncotarget, vol. 6, no. 24, pp. 20500-20512. https://doi.org/10.18632/oncotarget.3985

Tumorigenesis and peritoneal colonization from fallopian tube epithelium. / Eddie, Sharon L.; Quartuccio, Suzanne M.; hAinmhire, Eoghainin Ó.; Moyle-Heyrman, Georgette; Lantvit, Dan D.; Wei, Jian-Jun; Vanderhyden, Barbara C.; Burdette, Joanna E.

In: Oncotarget, Vol. 6, No. 24, 04.05.2015, p. 20500-20512.

Research output: Contribution to journalArticle

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Eddie SL, Quartuccio SM, hAinmhire EÓ, Moyle-Heyrman G, Lantvit DD, Wei J-J et al. Tumorigenesis and peritoneal colonization from fallopian tube epithelium. Oncotarget. 2015 May 4;6(24):20500-20512. https://doi.org/10.18632/oncotarget.3985