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Hypoxia-dependent expression of ADAM8 in human pancreatic cancer cell lines.

Authors: Valkovskaya, N.V.;

Hypoxia-dependent expression of ADAM8 in human pancreatic cancer cell lines.

Abstract

????????????????: ????????????????, ?????? ?????????????????????? ???????????? ?????????????????????????????? ???????????????? ???????????????? ???????????????????????????????? ????????????????, ???????????????????????? ???????????????? ???? ?????????????????????????????? ????????????????????. ?????? ?????????????????????????? ???????????? (??????) ???????????????? ?????????? ?????????????????????? ????????????????, ???????????????????? ?????????????? ???????????????????????? ?? ?????????????? ?? ?????????????????????? ?????????? ?? ????????????, ?????? ?????????????????????????? ???????????????????????????????????????? ???????????????????? ??????????????. ???????????????? ?????? ????????, ?????? ?????? ?????????????????? ?? ???????????????????????????????? ?? ?????????????? ???????????????? ????????????????. ????????: ???????????????????????? ?????????????????? ?????????????????????? ???????????????????? ?????????? ????????8 ?? ?????? ???????? ???? ???????????? ?????????????????????? ????????????. ?????????????????? ?? ????????????: ???????????????????????? ?????????????????? ?????????? ?????? ????????????????. ???????????????????? ???????? ?? ?????????? ADAM8 ???????????????????? ???????????????? qRTPCR ?? ??????????????-????????-?????????????? ????????????????????????????. ????????????????????: ??????????????????????, ?????? ???????????????? ???????????????????????? ?????????????????? ???????????? ???????? ??DAM8 ?? 2,5???5,9 ???????? ?? ?????????????????????????? ?????????????????? ???????????? ??????, ???? ?????????????????????? ???????????? ?????????? Panc-1. ?? ?????????????? ?????????? BxPC-3, Capan-1 ?? Su8686 ???????????????? ???????????????? ???????????????????????? ?????????????????????? ???????????? ???????????????????? ???????? ADAM8 ?????? ???????????????? (p = 0,046). ?? ?????????????? ??????????????-????????-?????????????? ????????????????, ?????? ???????????????????? ?????????????????? ?????????? ?????????????????? ADAM8 (90 kDa) ?????????????????????? ?? ?????????????????? ?????? ?????? ???????????????? ?? 5 ???? 8 ?????????????????? ?????????????????? ?????????? ??????. ???????????????? ???????????????????????? ?????????????????? ???????????????????? ???????????????????? ?????????? ADAM8 (60 kDa) ?? 4 ???? 8 ?????????????????? ?????????? ??????: Aspc-1, Colo-357, Panc-1, T3M4, ???????? ?????????????????? ?????????????????? ???????????????? ??????????????????????. ????????????: ?? ?????????????????? ???????????? ?????? ???????????????? ???????????????????? ???????????? ?????????????????? ?? ?????????????????? ?????? ???????????????? ???????????? ????????????????????, ?????? ????????, ?????? ?? ?????????? ADAM8, ?????? ?????????????????? ???????????????????????? ?????????????????????? ???????????????????? ???? ???????????? ?????????????????????? ?? ?????????????????????????? ???????? ADAM8 ?? ???????????????? ?? ???????????????????? ??????, ?????????????? ???????????????????? ?????????????? ???????????????? ???????????????????????????????? ????????????????.

One of the most characteristic features of malignant tissue is the high level of intratumoral hypoxia, which is considered as a powerful factor for induction of tumor aggressiveness and malignant progression. Pancreatic cancer (PC) is a near fatal disease with very unfavorable clinical outcome despite the application of different treatment regimes. It was shown that PC is characterized by high level of hypoxia. Aim: To clarify the correlation between tumor hypoxia and ADAM8 protein expression. Materials and Methods: ASPC-1, Panc-1, BxPC-3, Capan-1, MiaPaCa-2, Colo-357, Su8686 and T3M4 cell lines were used in the study. Expression of mRNA ADAM8 was evaluated by real-time quantitative polymerase chain reaction method. Immunoblot analysis was used to evaluate the expression of ADAM8 protein. Results: Hypoxia induced a 2.5???5.9-fold increase of ADAM8 mRNA levels of in the examined pancreatic cancer cell lines except Panc-1 (p = 0.046). On the protein level, hypoxia induced a 1.2???5.9-fold increase of the ADAM8 prodomain removal form (90 kDa) in 5/8 pancreatic cancer cells. Moreover, hypoxia induced a 1.3???2.0-fold increase of the remnant form ADAM8 (60 kDa) in 4/8 pancreatic cancer cell lines: Aspc-1, Colo-357, Panc-1, T3M4. Conclusion: It was observed the clear tendency in the increase both of ADAM8 mRNA and ADAM8 protein levels in pancreatic cancer cell lines under hypoxia compared to normal conditions of oxygenation. A potential role of ADAM8 as a hypoxia-dependent protein in the pathogenesis and evolution of pancreatic cancer that is characterized by high level of intratumoral hypoxia can be suggested.

Keywords

Reverse Transcriptase Polymerase Chain Reaction, Immunoblotting, Membrane Proteins, Cell Hypoxia, Gene Expression Regulation, Neoplastic, Oxygen, Pancreatic Neoplasms, ADAM Proteins, Cell Line, Tumor, Humans, Neoplasm Invasiveness, RNA, Messenger, Hypoxia, Uncategorized

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
10
Average
Average
Average
gold