PMID- 29263461 OWN - NLM STAT- MEDLINE DCOM- 20180725 LR - 20181202 IS - 1671-167X (Print) IS - 1671-167X (Linking) VI - 49 IP - 6 DP - 2017 Dec 18 TI - [Mechanism of cross talk between tissue factor/active coagulation factor VII and epidermal growth factor receptor signalings in colon cancer cells in culture]. PG - 931-936 AB - OBJECTIVE: To preliminarily verify the cross talk between tissue factor/active coagulation factor VII (TF/FVIIa) and epidermal growth factor receptor (EGFR) pathways in human colon cancer cells in culture. METHODS: FVIIa was treated to HT-29 (KRAS-wild type) and LoVo (KRAS-mutant) colon cancer cells to activate TF/FVIIa pathway, qRT-PCR and Western blot were used to detect the expressions of amphiregulin (AREG) and epiregulin (EREG), ligands of EGFR on mRNA and protein levels, respectively. After knocking down expression of TF by TF-targeted siRNA transfection, FVIIa was treated and mRNA expressions of AREG and EREG were detected to see whether the FVIIa-induced effects were dependent on TF. Expressions of mRNA of TF and FVII were detected by qRT-PCR following the activation of EGFR pathway by treatment with epidermal growth factor (EGF) to HT-29 and LoVo cells. RESULTS: After TF/FVIIa pathway was activated, for HT-29 cells, expressions of AREG (on mRNA level) and EREG (both on mRNA and protein level) were significantly down-regulated versus those of control group, gene expressions of AREG and EREG were 0.55+/-0.09 vs.0.99 +/-0.09, 0.67+/-0.10 vs.1.02+/-0.02, protein expressions of EREG were 0.54+/-0.09 vs.1.04+/-0.13, all P<0.05. For LoVo cells, expressions of AREG (both on mRNA and protein level) and EREG (on protein level) were significantly up-regulated versus those of control group, gene expression of AREG were 1.87+/-0.39 vs. 0.93+/-0.23, protein expressions of AREG and EREG were 3.09+/-0.73 vs.1.11+/-0.21, 1.53+/-0.19 vs.0.97+/-0.23, all P<0.05. The regulating effect of AREG and EREG mRNA expression by FVIIa in HT-29 and LoVo cells could both be partly blocked by knocking down TF expression. For HT-29 cells, activation of EGFR pathway induced no significant TF mRNA expression, FVII mRNA expression was not detected. However,for LoVo cells, activation of EGFR pathway induced significantly higher mRNA expressions of both TF and FVII, expressions were 1.53+/-0.23 vs.1.00+/-0.23, 53.20+/-6.08 vs.1.00+/-0.15, all P<0.05. CONCLUSION: In colon cancer cell LoVo, when activated, TF/FVIIa pathway and EGFR pathway could interact through upregulating the other pathway's effectors, and mutant KRAS might play a critical role in the two pathways' cross talk. FAU - Chen, H K AU - Chen HK AD - Department of General Surgery, Peking University First Hospital, Beijing 100034, China. FAU - Dai, Y AU - Dai Y AD - Department of Gastroenterology, Peking University First Hospital, Beijing 100034, China. FAU - Wu, T AU - Wu T AD - Department of Gastroenterology, Peking University First Hospital, Beijing 100034, China. FAU - Wang, X AU - Wang X AD - Department of General Surgery, Peking University First Hospital, Beijing 100034, China. FAU - Wan, Y L AU - Wan YL AD - Department of General Surgery, Peking University First Hospital, Beijing 100034, China. FAU - Tang, J Q AU - Tang JQ AD - Department of General Surgery, Peking University First Hospital, Beijing 100034, China. LA - chi PT - English Abstract PT - Journal Article PL - China TA - Beijing Da Xue Xue Bao Yi Xue Ban JT - Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences JID - 101125284 RN - 0 (Amphiregulin) RN - 0 (EREG protein, human) RN - 0 (Epiregulin) RN - 0 (RNA, Messenger) RN - 62229-50-9 (Epidermal Growth Factor) RN - 9001-25-6 (Factor VII) RN - 9035-58-9 (Thromboplastin) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Amphiregulin/physiology MH - Cell Count MH - Colonic Neoplasms/*metabolism MH - Epidermal Growth Factor MH - Epiregulin MH - ErbB Receptors/*physiology MH - Factor VII/*physiology MH - Humans MH - RNA, Messenger MH - Signal Transduction MH - *Thromboplastin EDAT- 2017/12/22 06:00 MHDA- 2018/07/26 06:00 CRDT- 2017/12/22 06:00 PHST- 2017/12/22 06:00 [entrez] PHST- 2017/12/22 06:00 [pubmed] PHST- 2018/07/26 06:00 [medline] PST - ppublish SO - Beijing Da Xue Xue Bao Yi Xue Ban. 2017 Dec 18;49(6):931-936.