PMID- 10761710 OWN - NLM STAT- MEDLINE DCOM- 20000420 LR - 20190513 IS - 0910-5050 (Print) IS - 1876-4673 (Electronic) IS - 0910-5050 (Linking) VI - 91 IP - 2 DP - 2000 Feb TI - Transforming growth factor-alpha induces the differentiation of sarcomatoid cholangiocarcinoma cells. PG - 223-30 AB - A sarcomatoid cholangiocarcinoma cell line, ETK-1, was established from a patient. Phenotypically, the cells corresponded to immature biliary epithelial cells. Because a small number of ETK-1 cells appeared to differentiate spontaneously along a biliary epithelial lineage in continuous culture, we examined the factors that initiate and/or promote the differentiation of the cells. Transforming growth factor-alpha (TGFalpha) induced significant changes in ETK-1 cells. After stimulation with the factor, ETK-1 cells displayed morphologic transformation at a much higher frequency, with the appearance of many large cells with intracytoplasmic vacuoles, and the production of mucinous substances. These morphologically transformed cells were phenotypically similar to well-differentiated adenocarcinoma cells. The expression pattern of integrins after TGFalpha treatment also supported the maturation of the ETK-1 cells. The antibody against the receptor of TGFalpha inhibited these changes by TGFalpha. Moreover, the proliferation rate of ETK-1 cells was suppressed by TGFalpha. Our data suggest that TGFalpha can act as a differentiation factor along a biliary epithelial lineage. FAU - Enjoji, M AU - Enjoji M AD - Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka. enjoji@intmed3.med.kyushu-u.ac.jp FAU - Nakashima, M AU - Nakashima M FAU - Nakamuta, M AU - Nakamuta M FAU - Nawata, H AU - Nawata H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Japan TA - Jpn J Cancer Res JT - Japanese journal of cancer research : Gann JID - 8509412 RN - 0 (Integrins) RN - 0 (Receptors, Fibroblast Growth Factor) RN - 0 (Transforming Growth Factor alpha) RN - 104781-85-3 (Fibroblast Growth Factor 1) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit) SB - IM MH - Bile Duct Neoplasms/*pathology MH - *Bile Ducts, Intrahepatic MH - Cell Differentiation/drug effects MH - Cholangiocarcinoma/*pathology MH - Fibroblast Growth Factor 1/pharmacology MH - Humans MH - Integrins/analysis MH - Proto-Oncogene Proteins c-kit/analysis MH - Receptors, Fibroblast Growth Factor/analysis MH - Transforming Growth Factor alpha/*pharmacology MH - Tumor Cells, Cultured PMC - PMC5926319 EDAT- 2000/04/13 09:00 MHDA- 2000/04/25 09:00 PMCR- 2000/02/01 CRDT- 2000/04/13 09:00 PHST- 2000/04/13 09:00 [pubmed] PHST- 2000/04/25 09:00 [medline] PHST- 2000/04/13 09:00 [entrez] PHST- 2000/02/01 00:00 [pmc-release] AID - CAE223 [pii] AID - 10.1111/j.1349-7006.2000.tb00935.x [doi] PST - ppublish SO - Jpn J Cancer Res. 2000 Feb;91(2):223-30. doi: 10.1111/j.1349-7006.2000.tb00935.x.