Mucinous adenocarcinoma developed from human fallopian tube epithelial cells through defined genetic modifications

Weiwei Shan, Imelda Mercado-Uribe, Jing Zhang, Daniel Rosen, Shiwu Zhang, Jianjun Wei, Jinsong Liu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Recent studies have suggested that some ovarian and pelvic serous carcinomas could originate from the fimbriated end of the distal fallopian tube. To test this hypothesis, we immortalized a normal human fallopian tube epithelial (FTE ) cell line by using retrovirus-mediated overexpression of the early region of the SV40 T/t antigens and the human telomerase reverse transcriptase subunit (hTE RT). These immortalized FTE s were then transformed by ectopic expression of oncogenic human HRASV12. Tumorigenicity of the immortalized and/or transformed cells was subsequently tested by anchorage-independence growth assay and inoculation into nude mice via subcutaneous and intraperitoneal injection. As expected, the HRAS V12-transformed FTE s produced tumors through both subcutaneous and intraperitoneal injections, whereas no tumor growth was observed in immortalized FTE s. Unexpectedly, histopathological examination of tumors resulting from subcutaneous as well as intraperitoneal injections revealed largely poorly differentiated mucinous adenocarcinoma mixed with undifferentiated carcinoma. The tumor implants invaded extensively to the liver, colon, spleen, omentum, adrenal gland and renal capsule. Immunohistochemical staining of tumor cells showed positive staining for the epithelial cell markers cytokeratin AE1/AE3 and Müllerian lineage marker PAX8. Our study demonstrates that FTE s can generate poorly differentiated mucinous adenocarcinoma mixed with undifferentiated carcinoma through genetic modifications. Thus, we provide the first experimental evidence that fimbrial epithelial cells of the fallopian tube could be a potential source of ovarian mucinous adenocarcinoma.

Original languageEnglish (US)
Pages (from-to)2107-2113
Number of pages7
JournalCell Cycle
Volume11
Issue number11
DOIs
StatePublished - Jun 1 2012

Keywords

  • Fallopian tube epithelial cells
  • Mucinous adenocarcinoma
  • Oncogene
  • Retrovirus
  • Transformation

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology
  • Developmental Biology

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