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    Wyświetlanie 1-8 z 8
    Tytuł:
    Targeting the hypoxia pathway in malignant plasma cells by using 17-allylamino-17-demethoxygeldanamycin
    Autorzy:
    Kocemba-Pilarczyk, Kinga
    Ostrowska, Barbara
    Trojan, Sonia
    Aslan, Ecce
    Kusior, Dorota
    Lasota, Małgorzata
    Lenouvel, Claire
    Dulińska-Litewka, Joanna
    Powiązania:
    https://bibliotekanauki.pl/articles/1038530.pdf
    Data publikacji:
    2018
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    Multiple myeloma
    HIF-1
    hypoxia
    17-AAG
    Opis:
    Multiple myeloma (MM) is characterized as a clonal expansion of malignant plasma cells in the bone marrow, which is often associated with pancytopenia and osteolytic bone disease. Interestingly, myeloma-infiltrated bone marrow is considered to be hypoxic, providing selection pressure for a developing tumour. Since HSP90 was shown to participate in stabilization of the subunit of the key transcription factor HIF-1, which controls the hypoxic response, the aim of this study was to investigate the influence of a HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG), on MM cells cultured under low oxygenation conditions. We confirmed that 17-AAG inhibits hypoxic induction of the HIF-1 target genes in malignant plasma cells and demonstrate the concentration range of severe hypoxia-specific cytotoxicity. Next, we selected the malignant plasma cells under severe hypoxia/re-oxygenation culture conditions in the presence or absence of 17-AAG and subsequently, the cells which survived were further expanded and analyzed. Interestingly, we have noticed significant changes in the survival and the response to anti-MM drugs between the parental cell lines and those selected in cyclic severe hypoxia in the presence and absence of 17-AAG. Importantly, we also observed that the lack of oxygen itself, irrespectively of HIF-1 inhibition, is the main/pivotal factor driving the selection process in the experiments presented here.
    Źródło:
    Acta Biochimica Polonica; 2018, 65, 1; 101-109
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Differential relationship between two hypoxia markers: HIF-1α and GLUT1 and classic prognostic factors in invasive breast carcinoma
    Zróżnicowana zależność pomiędzy dwoma markerami hipoksji: HIF-1α i GLUT1 a klasycznymi czynnikami prognostycznymi w inwazyjnym raku piersi
    Autorzy:
    Żyromska, Agnieszka
    Andrusewicz, Hanna
    Łysik, Joanna
    Jóźwicki, Wojciech
    Wiśniewski, Tomasz
    Powiązania:
    https://bibliotekanauki.pl/articles/1029826.pdf
    Data publikacji:
    2016
    Wydawca:
    Medical Communications
    Tematy:
    GLUT1
    HIF-1α
    hypoxia
    immunohistochemistry
    prognostic factors
    Opis:
    Background: Tumor hypoxia is an adverse prognostic factor which promotes cancer aggressiveness and limits its radio- and chemosensitivity. The aim of our study was to explore the relationship between endogenous hypoxia markers and classic prognostic factors, including clinical stage and the expression of ER, PR, and HER2 in primary untreated breast carcinoma. Methods: A retrospective immunohistochemical analysis of archived tissue blocks collected from 153 women, who underwent total mastectomy and lymph node dissection, included the expression of two hypoxia-related proteins: HIF-1α and GLUT1. Results: GLUT1 labelling index (LI) showed a positive correlation with T stage (R = 0.18, p = 0.026) and HER2 status (R = 0.25, p = 0.002), and a negative correlation with the expression of ER (R = −0.19, p = 0.017) and PR (R = −0.17, p = 0.032). HIF-1α LI showed a positive correlation with ER expression (R = 0.16, p = 0.045). In the multivariate regression analysis, a different relationship between classic prognostic factors and the two tested hypoxia proteins was proven. Higher GLUT1 expression correlated with ER and PR negativity (p = 0.02 and p = 0.01, respectively) as well as with higher expression of HER2 (p = 0.04). HIF-1α showed no association with PR and HER2, but a positive correlation with ER (p = 0.02). Neither of the hypoxia proteins was associated with a tumor grade. Only one clinical feature, T stage, correlated with both of the hypoxia markers: positively with GLUT1 (p = 0.049) and negatively with HIF-1α (p = 0.01) expression. Conclusions: In breast cancer, GLUT1 expression may be considered an additional prognostic factor which correlates with an adverse status of HER2 and hormonal receptors, and indicates a more hypoxic, radio- and chemotherapy refractory profile of carcinoma.
    Tło: Hipoksja w  guzie nowotworowym stanowi niekorzystny czynnik prognostyczny, ogranicza jego promienioi chemiowrażliwość oraz promuje bardziej agresywny przebieg choroby. Przewidywanie rokowania i odpowiedzi na leczenie wymaga wiedzy o związku hipoksji z uznanymi czynnikami prognostycznymi. Celem badania było określenie zależności pomiędzy endogennymi markerami hipoksji w  pierwotnym przewodowym raku piersi a  klasycznymi czynnikami prognostycznymi, takimi jak stopień zaawansowania klinicznego oraz ekspresja receptorów ER, PR i HER2. Metody: Retrospektywna analiza immunohistochemiczna archiwizowanych bloczków tkanek pobranych od 153 kobiet, poddanych mastektomii i limfadenektomii pachowej, objęła ekspresję dwóch związanych z hipoksją białek: HIF-1α i GLUT1. Wyniki: Indeks wiązania GLUT1 (GLUT1 LI) wykazał korelację dodatnią z wielkością guza (R = 0,18, p = 0,026) i ekspresją HER2 (R = 0,25, p = 0,002) oraz ujemną z ekspresją ER (R = −0,19, p = 0,017) i PR (R = −0,17, p = 0,032). HIF-1α LI korelował wyłącznie z ekspresją ER (R = 0,16, p = 0,045). W analizie wieloczynnikowej wykazano zróżnicowaną zależność pomiędzy klasycznymi czynnikami prognostycznymi i testowanymi markerami hipoksji. GLUT1 LI korelował negatywnie z ekspresją ER i PR (odpowiednio p = 0,02 i p = 0,01) oraz pozytywnie z ekspresją HER2 (p = 0,04). Nie udowodniono korelacji pomiędzy HIF-1α LI a ekspresją PR czy HER2, natomiast wykazano jego dodatnią zależność z ekspresją ER (p = 0,02). Żaden marker hipoksji nie korelował ze stopniem zróżnicowania histologicznego nowotworu. Tylko jeden kliniczny czynnik – wielkość guza (T) – korelował z ekspresją badanych białek: dodatnio z GLUT1 (p = 0,049), a ujemnie z HIF-1α (p = 0,01). Wnioski: Ekspresja GLUT1 w raku piersi może stanowić dodatkowy czynnik prognostyczny, korelujący z niekorzystnym statusem receptora HER2 i receptorów hormonalnych oraz wskazywać na bardziej hipoksyczny, oporny na radioi chemioterapię, profil raka.
    Źródło:
    Current Gynecologic Oncology; 2016, 14, 4; 197-203
    2451-0750
    Pojawia się w:
    Current Gynecologic Oncology
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Effect of different intensities aerobic exercise to cardiac angiogenesis regulation on Wistar rats
    Autorzy:
    Sylviana, N.
    Goenawan, H.
    Susanti, Y.
    Lesmana, R.
    Megantara, I.
    Setiawan
    Powiązania:
    https://bibliotekanauki.pl/articles/16539096.pdf
    Data publikacji:
    2022
    Wydawca:
    Polska Akademia Nauk. Czasopisma i Monografie PAN
    Tematy:
    angiogenesis
    exercise
    CD34+
    HIF-1α
    myocardium
    PGC-1α
    VEGF
    Opis:
    The adaptation response of myocardium angiogenesis stimulated by specific exercise intensities remains unclear. The aims of this study is to explore the effect of different intensities aerobic exercise to cardiac angiogenesis regulation via HIF-1α, PGC-1α, VEGF, and CD34+ in Wistar rats. Wistar rats were divided into control and exercise groups. Exercise groups were trained on a treadmill for 12 weeks, 30 min/day for 5 days with low, moderate, and high-intensity groups. The rats were sacrificed, and the myocardium was collected and preserved at -80°C until used. Cardiac protein samples were extracted and run for Western blotting using the specific antibodies: hypoxia-inducible factor (HIF)-1α, Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), vascular endothelial growth factor (VEGF), and Cluster of differentiation 34 (CD34+). Results showed that protein expression of HIF-1α, PGC-1α, VEGF, and CD34+ was increased significantly by different intensities in the exercise group compared to the control. A correlation statistics test showed that there was a strong correlation effect of HIF-1α on VEGF protein expression in low (p=0.047) and high intensity exercise groups (p=0.009), but no effect was found in the moderate groups. In addition, there was a significant strong effect of PGC-1α on VEGF protein expression in the moderate groups (p=0.037), but no effect was found in other groups. In conclusion, different exercise intensities induce a different modulation pattern of proteins which might be responsible for cardiac adaptation, especially angiogenesis.
    Źródło:
    Polish Journal of Veterinary Sciences; 2022, 25, 1; 119-128
    1505-1773
    Pojawia się w:
    Polish Journal of Veterinary Sciences
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Expression and hypoxia-responsiveness of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 in mammary gland malignant cell lines
    Autorzy:
    Minchenko, Oleksandr
    Opentanova, Iryna
    Ogura, Tsutomu
    Minchenko, Dmytro
    Komisarenko, Sergiy
    Caro, Jaime
    Esumi, Hiroyasu
    Powiązania:
    https://bibliotekanauki.pl/articles/1041336.pdf
    Data publikacji:
    2005
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    dimethyloxalylglycine
    hypoxia
    mammary gland cancer cell lines
    PFKFB4
    HIF-1
    Opis:
    Recently, we have shown that PFKFB4 gene which encodes the testis isoenzyme of PFKFB is also expressed in the prostate and hepatoma cancer cell lines. Here we have studied expression and hypoxic regulation of the testis isoenzyme of PFKFB4 in several malignant cell lines from a female organ - the mammary gland. Our studies clearly demonstrated that PFKFB4 mRNA is also expressed in mammary gland malignant cells (MCF-7 and T47D cell lines) in normoxic conditions and that hypoxia strongly induces it expression. To better understand the mechanism of hypoxic regulation of PFKFB4 gene expression, we used dimethyloxalylglycine, a specific inhibitor of HIF-1α hydroxylase enzymes, which strongly increases HIF-1α levels and mimics the effect of hypoxia. It was observed that PFKFB4 expression in the MCF7 and T47D cell lines was highly responsive to dimethyloxalylglycine, suggesting that the hypoxia responsiveness of PFKFB4 gene in these cell lines is regulated by HIF-1 proteins. Moreover, desferrioxamine and cobalt chloride, which mimic the effect of hypoxia by chelating or substituting for iron, had a similar stimulatory effect on the expression of PFKFB mRNA. In other mammary gland malignant cell lines (BT549, MDA-MB-468, and SKBR-3) hypoxia and hypoxia mimics also induced PFKFB4 mRNA, but to variable degrees. The hypoxic induction of PFKFB4 mRNA was equivalent to the expression of PFKFB3, Glut1, and VEGF, which are known HIF-1-dependent genes. Hypoxia and dimethyloxalylglycine increased the PFKFB4 protein levels in all cell lines studied except MDA-MB-468. Through site-specific mutagenesis in the 5'-flanking region of PFKFB4 gene the hypoxia response could be limited. Thus, this study provides evidence that PFKFB4 gene is also expressed in mammary gland cancer cells and strongly responds to hypoxia via an HIF-1α dependent mechanism. Moreover, the PFKFB4 and PFKFB3 gene expression in mammary gland cancer cells has also a significant role in the Warburg effect which is found in all malignant cells.
    Źródło:
    Acta Biochimica Polonica; 2005, 52, 4; 881-888
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    The role of oligochitosans in akt kinase regulation
    Autorzy:
    Ignacak, Jan
    Wiśniewska-Wrona, Maria
    Dulińska-Litewka, Joanna
    Pałka, Iwona
    Kucharska, Magdalena
    Powiązania:
    https://bibliotekanauki.pl/articles/1034912.pdf
    Data publikacji:
    2015
    Wydawca:
    Sieć Badawcza Łukasiewicz - Polskie Towarzystwo Chitynowe
    Tematy:
    Akt kinase – PKB
    EAT cells proliferation
    HIF-1 factor.
    M2 pyruvate kinase
    Opis:
    Among characteristic properties of cancers, there is their increased glycolytic activity.Contrary to normal cells, neoplastic cells use anaerobic glycolysis, even when a sufficient amount of oxygen is available. The intensity of the process is associated with a considerable demand for energy in the form of ATP. Akt, which - acting through the mTOR pathway - activates the HIF-1 factor, which in turn activates hexokinase that participates in glucose phosphorylation, stimulates the transport of glucose to cells via increasing glucose transporters (GLUT) and activates lactate dehydrogenase (which transforms pyruvate to lactate). Chitosan, as well as products of its degradation - oligochitosans - contribute to inhibiting the activity of the Akt kinase, and thus contribute to inhibiting excessive glycolytic activity of Ehrlich ascites tumor (EAT) cells and to decreasing proliferation of these cells.
    Źródło:
    Progress on Chemistry and Application of Chitin and its Derivatives; 2015, 20; 73-81
    1896-5644
    Pojawia się w:
    Progress on Chemistry and Application of Chitin and its Derivatives
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Wybrane czynniki prognostyczne w raku jajnika
    Selected prognostic factors in ovarian cancer
    Autorzy:
    Markowska, Janina
    Bednarek, Wiesława
    Markowska, Anna
    Powiązania:
    https://bibliotekanauki.pl/articles/1030778.pdf
    Data publikacji:
    2010
    Wydawca:
    Medical Communications
    Tematy:
    BRCA1
    VEGF
    prognostic factors in ovarian cancer
    targeted therapy
    mRNA
    markery prognostyczne w raku jajnika
    terapia celowana
    hif-1α
    Opis:
    The authors discuss several predictive factors related to ovarian cancer, both those associated with prognosis and those potentially useful in targeted therapy thereof. Expression of mRNA BRCA1, VEGF and its receptors, CXCR4, HER-2, HIF-1α, COX-2, NM-23, KAI 1, IGF-1R, kisspeptin, neuropilin and Prox-1 gene are discussed. Expression of mRNA BRCA1 is associated not only with hereditary ovarian cancer, but also with its sporadic form. Higher expression correlates with a better response to taxanes. Hopefully, mRNA BRCA1 level in women with sporadic ovarian cancer will become a useful parameter, qualifying patients for a particular chemotherapy protocol. BRMS1 acts as a gene inhibiting development of metastases in ovarian cancer. Levels of mRNA for BRMS1 are lower in late than in early stage ovarian cancer. The VEFG family is involved in angio- and lymphangiogenesis and includes 5 glycoproteins (VEGF-A, VEGF-B, VEGF-C, VEGF-D and VEGF-E), which acting upon receptors VEGFR1-3. Neuropilin 1 plays a role in angiogenesis, while neuropilin 2 modulates lymphangiogenesis, similar to the Prox-1 gene. COX-2 mediates the release of pro-angiogenic factors. HIF-1α expression is associated with resistance of hypoxic cancer cells against cytostatics and radiation. Expression of c-Met correlates with poorly differentiated cancer types. The SDF-1/CXCR4 complex plays a key role in the development of cancer metastases. Survivin is present in cancer cells only, where it inhibits apoptosis and promotes the development of cancer. Metastases suppressor gene (BRMS1) and receptors for VEGF, CXCR4, HER-2, HIF-1α and COX-2, may serve as targets for targeted therapy. At present, an increasing number of studies focus on VEGF receptors. Poor expression of NM-23 and KAI 1 correlate with tumor ability to form metastases. The authors discuss the role of biological markers for clear-cell ovarian cancer (IGF-1R and kisspeptin). Promising topics for future studies are survivin, neuropilin and the Prox-1 gene.
    W artykule omówiono szereg czynników prognostycznych związanych nie tylko z rokowaniem, ale również z możliwością zastosowania terapii tarczowej w raku jajnika. Przedstawiono ekspresję mRNA BRCA1, VEGF i jego receptorów, CXCR4, HER-2, HIF-1α, COX-2, NM-23, KAI 1, IGF-1R, kisspeptyny, neuropiliny i genu Prox-1. Ekspresja mRNA BRCA1 wiąże się nie tylko z dziedzicznym rakiem jajnika, ale również z rakiem sporadycznym. Wyższa ekspresja powoduje lepszą odpowiedź na taksany. Przypuszcza się, że zawartość mRNA BRCA1 u kobiet z rakiem sporadycznym może służyć do selekcji pacjentek do odpowiedniego typu chemioterapii. BRMS1 działa jako gen hamowania przerzutów w raku jajnika. Poziomy mRNA dla BRMS1 są niższe w zaawansowanych stadiach raka niż we wczesnych. Rodzina VEGF związana z angiogenezą i limfangiogenezą składająca się z 5 glikoprotein (VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E) działa poprzez receptory VEGFR1-3. Neuropilina 1 odgrywa rolę w angiogenezie, a typ drugi moduluje proces limfangiogenezy, podobnie jak gen Prox-1. W uwalnianiu czynników proangiogennych bierze udział COX-2. Ekspresja HIF-1α związana jest z opornością niedotlenionych komórek raka na leczenie chemiczne i napromienianiem. Ekspresja c-Met wiąże się z niższym zróżnicowaniem raka. Kompleks SDF-1/CXCR4 odgrywa kluczową rolę w tworzeniu przerzutów komórek nowotworowych. Surwiwina występująca wyłącznie na komórkach nowotworowych poprzez hamowanie apoptozy promuje rozwój raka. Gen supresji przerzutów (BRMS1), podobnie jak receptory VEGF, CXCR4, HER-2, HIF-1α, COX-2, może być tarczą dla terapii celowanej. Obecnie coraz więcej badań dotyczy inhibitorów VEGF. Obniżona ekspresja NM-23 oraz KAI 1 koreluje ze zdolnością do przerzutowania. Omówiono markery biologiczne dla raka jasnokomórkowego jajnika (IGF-1R i kisspeptynę). Ciekawym obiektem badań może być surwiwina, neuropilina i gen Prox-1.
    Źródło:
    Current Gynecologic Oncology; 2010, 8, 1; 8-20
    2451-0750
    Pojawia się w:
    Current Gynecologic Oncology
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Nowe markery w raku jajnika
    New markers in ovarian cancer
    Autorzy:
    Markowska, Anna
    Jaszczyńska-Nowinka, Karolina
    Powiązania:
    https://bibliotekanauki.pl/articles/1031069.pdf
    Data publikacji:
    2012
    Wydawca:
    Medical Communications
    Tematy:
    CA-125
    E-cadherin
    E-kadheryna
    HE4
    HIF-1α
    KiSS-1
    ROMA
    SDF-1
    YKL-40
    markery raka jajnika
    ovarian cancer markers
    Opis:
    Neoplastic markers represent high molecular weight substances produced both by neoplastic and healthy cells in response to a developing tumor. A marker may also involve any assayable substance in tumor tissue which manifests immunoreactivity distinct from that in normal tissues. Neoplastic markers serve in the detection of the disease, monitoring of treatment efficacy and in the detection of a relapse. In the case of ovarian cancer, the most recognizable marker involves CA-125, an elevated level of which is detected in around 80% serous carcinomas andwhich increases as the disease progresses. Early stages of ovarian carcinomas are detected by estimation of HE4 (human epididymis protein). The Risk of Malignancy Index (RMI algorithm) is based on the estimation of the CA-125 level, transvaginal ultrasound examination and condition of menopause. Other algorithms used in ovarian carcinoma include OVA-1, based also on CA-125 level, menopausal status and on four proteomic markers, and ROMA (Risk of Ovarian Malignancy Algorithm), based on CA-125 and HE4. Other markers of less pronounced importance for ovarian carcinoma include: • CA-19-9 (antigen of gastrointestinal carcinoma) – of particular use in carcinomas of gastrointestinal tract, including pancreatic carcinoma but also mucous ovarian carcinoma; • CEA (carcinoembryonic antigen) – a marker of alimentary tract carcinomas, including colorectal carcinoma, gastric carcinoma but also mucous ovarian carcinoma; • CA-15-3 (MUC1) – the recognized marker of breast carcinoma, the concentration of which increases in advanced stages of ovarian carcinoma; • YKL-40 (glycoprotein of human cartilage) – allowing detection of early stages of ovarian carcinoma and its relapses; • kisspeptin (KiSS-1) – associated with the inhibition of metastases in clarocellular ovarian carcinoma; • HIF-1α (hypoxia-inducible factor-1α) – similarly to clusterin, linked to resistance to chemotherapy; • E-cadherin, SDF-1 and metadherin linked to the development of metastases; • enzymatic markers COX-1 and in particular COX-2 correlate with the progress of the disease while an increased COX-2 level indicates resistance to chemotherapy.
    Markery nowotworowe są wielkocząsteczkowymi substancjami wytwarzanymi w odpowiedzi na rozwijający się nowotwór zarówno przez komórki nowotworowe, jak i komórki zdrowe. Markerem może być także substancja oznaczona w tkance guza, która wykazuje inną immunoreaktywność niż w tkankach zdrowych. Markery nowotworowe służą do wykrycia choroby, monitorowania skuteczności leczenia, a także wykrycia wznowy. Najbardziej uznanym markerem dla raka jajnika jest CA-125, którego podwyższone stężenie występuje w około 80% raków surowiczych i wzrasta wraz z zaawansowaniem choroby. Do wykrycia wczesnych stadiów raka jajnika stosuje się HE4 (human epididymis protein). Na wartości stężenia CA-125, badaniu przezpochwowym i stanie menopauzalnym oparty jest algorytm RMI (Risk of Malignancy Index). Innymi algorytmami stosowanymi w raku jajnika są OVA-1 (oparty również na wartości CA-125, stanie menopauzalnym i czterech markerach proteomicznych) oraz ROMA (Risk of Ovarian Malignancy Algorithm), włączający do badania wartość CA-125 i HE4. Markerami mającymi mniejsze znaczenie w raku jajnika są: • CA-19-9 (gastrointestinal cancer antigen) – stosowany w rakach przewodu pokarmowego (w tym raku trzustki), ale również w raku śluzowym jajnika; • CEA (carcinoembryonic antigen) – marker dla raków przewodu pokarmowego, w tym raka jelita grubego i żołądka, ale też raka śluzowego jajnika; • CA-15-3 (MUC1) – uznany marker dla raka piersi, którego stężenie wzrasta w zaawansowanych stadiach raka jajnika; • YKL-40 (ludzka chrząstkowa glikoproteina) – wykrywająca wczesne stadia raka jajnika i jego wznowy; • kisspeptyna (KiSS-1) – związana z hamowaniem przerzutowania w jasnokomórkowym raku jajnika; • HIF-1α (hypoxia-inducible factor-1α) – związany z opornością na leczenie chemiczne, podobnie jak klusteryna; • E-kadheryna, SDF-1 (stromal-derived factor-1) i metadheryna – związane są z przerzutowaniem; • markery enzymatyczne COX-1 i COX-2 – korelują z progresją choroby, a wzrost stężenia COX-2 świadczy o oporności na chemioterapię.
    Źródło:
    Current Gynecologic Oncology; 2012, 10, 2; 116-123
    2451-0750
    Pojawia się w:
    Current Gynecologic Oncology
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Hypoxic regulation of PFKFB-3 and PFKFB-4 gene expression in gastric and pancreatic cancer cell lines and expression of PFKFB genes in gastric cancers
    Autorzy:
    Bobarykina, Anastasiya
    Minchenko, Dmytro
    Opentanova, Iryna
    Moenner, Michel
    Caro, Jaime
    Esumi, Hiroyasu
    Minchenko, Oleksandr
    Powiązania:
    https://bibliotekanauki.pl/articles/1041176.pdf
    Data publikacji:
    2006
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    MKN-45
    hypoxia
    PFKFB-3
    gastric cancer
    HIF
    Panc1
    PFKFB-4
    Opis:
    Previously we have shown that hypoxia strongly induces the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 and -4 (PFKFB-3 and PFKFB-4) genes in several cancer cell lines via a HIF-dependent mechanism. In this paper we studied the expression and hypoxic regulation of PFKFB-4 and PFKFB-3 mRNA as well as its correlation with HIF-1α, HIF-2α, VEGF and Glut1 mRNA expression in the pancreatic cancer cell line Panc1 and two gastric cancer cell lines MKN45 and NUGC3. This study clearly demonstrated that PFKFB-3 and PFKFB-4 mRNA are expresses in MKN45, NUGC3 and Panc1 cancers cells and that both genes are responsive to hypoxia in vitro. However, their basal level of expression and hypoxia responsiveness vary in the different cells studied. Particularly, PFKFB-3 mRNA is highly expressed in MKN45 and NUGC3 cancer cells, with the highest response to hypoxia in the NUGC3 cell line. The PFKFB-4 mRNA has a variable low basal level of expression in both gastric and pancreatic cancer cell lines. However, the highest hypoxia response of PFKFB-4 mRNA is found in the pancreatic cancer cell line Panc1. The basal level of PFKFB-4 protein expression is the highest in NUGC3 gastric cancer cell line and lowest in Panc1 cells, with the highest response to hypoxia in the pancreatic cancer cell line. Further studies showed that PFKFB-3 and PFKFB-4 gene expression was highly responsive to the hypoxia mimic dimethyloxalylglycine, a specific inhibitor of HIF-α hydroxylase enzymes, suggesting that the hypoxia responsiveness of PFKFB-3 and PFKFB-4 genes in these cell lines is regulated by the HIF transcription complex. The expression of VEGF and Glut1, which are known HIF-dependent genes, is also strongly induced under hypoxic conditions in gastric and pancreatic cancer cell lines. The levels of HIF-1α protein are increased in both gastric and pancreatic cancer cell lines under hypoxic conditions. However, the basal level of HIF-1α as well as HIF-2α mRNA expression and their hypoxia responsiveness are different in the MKN45 and NUGC3 cancer cells. Thus, the expression of HIF-1α mRNA is decreased in both gastric cancer cell lines treated by hypoxia or dimethyloxalylglycine, but HIF-2α mRNA expression is not changed significantly in NUGC3 and slightly increased in MKN45 cells. Expression of PFKFB-4 and PFKFB-3 was also studied in gastric cancers and corresponding nonmalignant tissue counterparts from the same patients on both the mRNA and protein levels. The expression of PFKFB-3 and PFKFB-4 mRNA as well as PFKFB-1 and PFKFB-2 mRNA was observed in normal human gastric tissue and was increased in malignant gastric tumors. The basal level of PFKFB-4 protein expression in gastric cancers was much higher as compared to the PFKFB-3 isoenzyme. In conclusion, this study provides evidence that PFKFB-4 and PFKFB-3 genes are also expressed in gastric and pancreatic cancer cells, they strongly respond to hypoxia via a HIF-1α dependent mechanism and, together with the expression of PFKFB-1 and PFKFB-2 genes, possibly have a significant role in the Warburg effect which is found in malignant cells.
    Źródło:
    Acta Biochimica Polonica; 2006, 53, 4; 789-799
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
      Wyświetlanie 1-8 z 8

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