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

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 (hTERT). These immortalized FTEs were then transformed by ectopic expression of oncogenic human HRAS (V12) . 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 FTEs produced tumors through both subcutaneous and intraperitoneal injections, whereas no tumor growth was observed in immortalized FTEs. 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 FTEs 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.

• Authors: Weiwei Shan, Imelda Mercado-Uribe, Jing Zhang, Daniel Rosen, Shiwu Zhang, Jianjun Wei, Jinsong Liu
• Journal: Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 11 Issue 11 Pg. 2107-13 (Jun 01 2012) ISSN: 1551-4005 [Electronic] United States
• PMID: 22592533 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Polyomavirus Transforming
• PAX8 Transcription Factor
• Paired Box Transcription Factors
• Pax8 protein, mouse
• Keratins
• TERT protein, human
• Telomerase
• HRAS protein, human
• Proto-Oncogene Proteins p21(ras)

Topics

• Adenocarcinoma, Mucinous (genetics, metabolism, pathology)
• Animals
• Antigens, Polyomavirus Transforming (genetics, metabolism)
• Carcinoma (metabolism, pathology)
• Carcinoma, Ovarian Epithelial
• Cell Line, Transformed
• Cell Transformation, Neoplastic
• Epithelial Cells (cytology, metabolism)
• Fallopian Tubes (cytology)
• Female
• Humans
• Immunohistochemistry
• Keratins (metabolism)
• Mice
• Mice, Nude
• Neoplasms, Glandular and Epithelial (genetics, metabolism, pathology)
• Ovarian Neoplasms (genetics, metabolism, pathology)
• PAX8 Transcription Factor
• Paired Box Transcription Factors (metabolism)
• Proto-Oncogene Proteins p21(ras) (genetics, metabolism)
• Telomerase (genetics, metabolism)