Skip to main content
Erschienen in: Tumor Biology 6/2011

01.12.2011 | Research Article

The expression of p33ING1, p53, and autophagy-related gene Beclin1 in patients with non-small cell lung cancer

verfasst von: Jun Liu, Yongping Lin, Haihong Yang, Qiuhua Deng, Guoqin Chen, Jianxing He

Erschienen in: Tumor Biology | Ausgabe 6/2011

Einloggen, um Zugang zu erhalten

Abstract

The purpose of this study was to investigate the expressions of tumor inhibitor of growth (ING1) gene p33ING1, p53, and autophagy-related gene Beclin1 in human non-small cell lung cancer (NSCLC), and the correlation between their expressions with clinical pathological features and clinical significance. The research can provide new ideas and experimental evidence for early diagnosis and biotherapy for NSCLC in the future. The human NSCLC tissues and surrounding non-cancerous tissues were collected from surgical operation. The expressions of mRNA or protein of p33ING1, p53, and Beclin1 were detected by using of reverse transcription polymerase chain reaction or Western blot in these tissues. The results were used to analyze the relationships between these gene expressions with the developing of NSCLC and clinical pathological features. The expressions of mRNA or protein of p33ING1 and Beclin1 in NSCLC tissues were significantly lower than that in surrounding noncancerous tissues (p < 0.05). The expressions of mRNA or protein of p33ING1 and Beclin1 in well- and middle-differentiated NSCLC tissues were lower than those in poor-differentiated NSCLC tissues (p < 0.05). The expressions of mRNA or protein of p33ING1 and Beclin1 in presence of lymph nodes metastasis were lower than those in absence of lymph nodes metastasis (p < 0.05). The expressions of mRNA or protein of p33ING1 and Beclin1 in patients of pathological stage (stages I–II) were higher than those in pathological stage (stages III–IV) (p < 0.05). But the expression of protein of mutant-type p53 in NSCLC tissues was significantly higher than that in surrounding non-cancerous tissues (p < 0.05). The expressions of protein of mutant-type p53 in well- and middle-differentiated NSCLC tissues were higher than those in poor-differentiated NSCLC tissues (p < 0.05). The expressions of protein of mutant-type p53 in presence of lymph nodes metastasis were higher than those in absence of lymph nodes metastasis (p < 0.05). The expressions of protein of mutant-type p53 in patients of pathological stage (stages I–II) were lower than those in pathological stage (stages III–IV) (p < 0.05). These expression changes of p33ING1, p53, and autophagy-related Beclin1 genes were associated with tumor cell differentiation, lymph nodes metastasis, and pathological stage of NSCLC. But these expression changes of these three genes were not associated with gender, age, size of primary carcinoma, histological type of NSCLC (p > 0.05). The expression of mRNA of p53 and Beclin1 were correlated with p33ING1 mRNA expression in NSCLC tissues (p < 0.05). The activity changes of tumor inhibitor of growth, autophagy, and apoptosis may be related to the emergence and the development of NSCLC. The combined detection of p33ING1, p53, and Beclin1 genes and proteins will be helpful for early diagnosis and prognosis judgment for NSCLC, and can provide experimental evidence for biotherapy of NSCLC.
Literatur
1.
Zurück zum Zitat Smith CB, kelley AS, Meier DE. Evidence for new standard of care in non-small cell lung cancer patients. Semin Thorac Cardiovasc Surg. 2010;22:193–4.PubMedCrossRef Smith CB, kelley AS, Meier DE. Evidence for new standard of care in non-small cell lung cancer patients. Semin Thorac Cardiovasc Surg. 2010;22:193–4.PubMedCrossRef
2.
Zurück zum Zitat McKeage MJ, Jameson MB, AS1404-201 Study Group Investigators. Comparative outcomes of squamous and non-squamous non-small cell lung cancer (NSCLC) patients in phase II studies of ASA404 (DMXAA) – retrospective analysis of pooled data. J Thorac Dis. 2010;2:199–204. McKeage MJ, Jameson MB, AS1404-201 Study Group Investigators. Comparative outcomes of squamous and non-squamous non-small cell lung cancer (NSCLC) patients in phase II studies of ASA404 (DMXAA) – retrospective analysis of pooled data. J Thorac Dis. 2010;2:199–204.
3.
Zurück zum Zitat Korpanty G, Smyth E, Carney DN. Update on anti-angiogenic therapy in non-small cell lung cancer: are we making progress? J Thorac Dis. 2011;3:19–29. Korpanty G, Smyth E, Carney DN. Update on anti-angiogenic therapy in non-small cell lung cancer: are we making progress? J Thorac Dis. 2011;3:19–29.
4.
Zurück zum Zitat Shao WL, Wang DY, He JX. The role of gene expression profiling in early-stage non-small cell lung cancer. J Thorac Dis. 2010;2:89–99. Shao WL, Wang DY, He JX. The role of gene expression profiling in early-stage non-small cell lung cancer. J Thorac Dis. 2010;2:89–99.
5.
Zurück zum Zitat Shash E, Peccatori FA, Azim Jr HA. Optimizing the use of epidermal growth factor receptor inhibitors in advanced non-small-lung cancer (NSCLC). J Thorac Dis. 2011;3:57–64. Shash E, Peccatori FA, Azim Jr HA. Optimizing the use of epidermal growth factor receptor inhibitors in advanced non-small-lung cancer (NSCLC). J Thorac Dis. 2011;3:57–64.
6.
Zurück zum Zitat Xiao DK, He JX. Epithelial mesenchymal transition and lung cancer. J Thorac Dis. 2010;2:154–9. Xiao DK, He JX. Epithelial mesenchymal transition and lung cancer. J Thorac Dis. 2010;2:154–9.
7.
Zurück zum Zitat Yang HH, Zhang Q, He JX, Lu WJ. Regulation of calcium signaling in lung cancer. J Thorac Dis. 2010;2:52–6. Yang HH, Zhang Q, He JX, Lu WJ. Regulation of calcium signaling in lung cancer. J Thorac Dis. 2010;2:52–6.
8.
Zurück zum Zitat Athar M, Elmets CA, Kopelovich L. Pharmacological activation of p53 in cancer cells. Curr Pharm Des. 2011;17:631–9.PubMed Athar M, Elmets CA, Kopelovich L. Pharmacological activation of p53 in cancer cells. Curr Pharm Des. 2011;17:631–9.PubMed
9.
Zurück zum Zitat Muller PA, Vousden KH, Norman JC. p53 and its mutants in tumor cell migration and invasion. J Cell Biol. 2011;192:209–18.PubMedCrossRef Muller PA, Vousden KH, Norman JC. p53 and its mutants in tumor cell migration and invasion. J Cell Biol. 2011;192:209–18.PubMedCrossRef
10.
Zurück zum Zitat Giatromanolaki A, Koukourakis MI, Kakolyris S, Turley H, O'Byrne K, Scott PA, et al. Vascular endothelial growth factor, wild-type p53, and angiogenesis in early operable non-small cell lung cancer. Clin Cancer Res. 1998;4:3017–24.PubMed Giatromanolaki A, Koukourakis MI, Kakolyris S, Turley H, O'Byrne K, Scott PA, et al. Vascular endothelial growth factor, wild-type p53, and angiogenesis in early operable non-small cell lung cancer. Clin Cancer Res. 1998;4:3017–24.PubMed
11.
Zurück zum Zitat Ozaki T, Nakagawara A. p53: the attractive tumor suppressor in the cancer research field. J Biomed Biotechnol. 2011;2011:603925.PubMedCrossRef Ozaki T, Nakagawara A. p53: the attractive tumor suppressor in the cancer research field. J Biomed Biotechnol. 2011;2011:603925.PubMedCrossRef
12.
Zurück zum Zitat Garkavtsev I, Kazarov A, Gudkov A, Riabowol K. Suppression of the novel growth inhibitor p33ING1 promotes neoplastic transformation. Nat Genet. 1996;14:415–20.PubMedCrossRef Garkavtsev I, Kazarov A, Gudkov A, Riabowol K. Suppression of the novel growth inhibitor p33ING1 promotes neoplastic transformation. Nat Genet. 1996;14:415–20.PubMedCrossRef
13.
Zurück zum Zitat Garkavtsev I, Demetrick D, Riabowol K. Cellular localization and chromosome mapping of a novel candidate tumor suppressor gene (ING1). Cytogenet Cell Genet. 1997;76:176–8.PubMedCrossRef Garkavtsev I, Demetrick D, Riabowol K. Cellular localization and chromosome mapping of a novel candidate tumor suppressor gene (ING1). Cytogenet Cell Genet. 1997;76:176–8.PubMedCrossRef
14.
Zurück zum Zitat Zeremski M, Horrigan SK, Grigorian IA, Westbrook CA, Gudkov AV. Localization of the candidate tumor suppressor gene ING1 to human chromosome 13q34. Somat Cell Mol Genet. 1997;23:233–6.PubMedCrossRef Zeremski M, Horrigan SK, Grigorian IA, Westbrook CA, Gudkov AV. Localization of the candidate tumor suppressor gene ING1 to human chromosome 13q34. Somat Cell Mol Genet. 1997;23:233–6.PubMedCrossRef
15.
Zurück zum Zitat Jager D, Stockert E, Scanlan MJ, Gure AO, Jager E, Knuth A, et al. Cancer-testis antigens and ING1 tumor suppressor gene product are breast cancer antigens: characterization of tissue-specific ING1 transcripts and a homologue gene. Cancer Res. 1999;59:6197–204.PubMed Jager D, Stockert E, Scanlan MJ, Gure AO, Jager E, Knuth A, et al. Cancer-testis antigens and ING1 tumor suppressor gene product are breast cancer antigens: characterization of tissue-specific ING1 transcripts and a homologue gene. Cancer Res. 1999;59:6197–204.PubMed
16.
Zurück zum Zitat Saito A, Furukawa T, Fukushige S, Koyama S, Hoshi M, Hayashi Y, et al. p24/ING1-ALT1 and p47/ING1-ALT2, distinct alternative transcripts of p33/ING1. J Hum Genet. 2000;45:177–81.PubMedCrossRef Saito A, Furukawa T, Fukushige S, Koyama S, Hoshi M, Hayashi Y, et al. p24/ING1-ALT1 and p47/ING1-ALT2, distinct alternative transcripts of p33/ING1. J Hum Genet. 2000;45:177–81.PubMedCrossRef
17.
Zurück zum Zitat Gunduz M, Demircan K, Gunduz E, Katase N, Tamamura R, Nagatsuka H. Potential usage of ING family members in cancer diagnostics and molecular therapy. Curr Drug Targets. 2009;10:465–76.PubMedCrossRef Gunduz M, Demircan K, Gunduz E, Katase N, Tamamura R, Nagatsuka H. Potential usage of ING family members in cancer diagnostics and molecular therapy. Curr Drug Targets. 2009;10:465–76.PubMedCrossRef
18.
Zurück zum Zitat Menendez C, Abad M, Gomez-Cabello D, Moreno A, Palmero I. ING proteins in cellular senescence. Curr Drug Targets. 2009;10:406–17.PubMedCrossRef Menendez C, Abad M, Gomez-Cabello D, Moreno A, Palmero I. ING proteins in cellular senescence. Curr Drug Targets. 2009;10:406–17.PubMedCrossRef
19.
Zurück zum Zitat Shah S, Smith H, Feng X, Rancourt DE, Riabowol K. ING function in apoptosis in diverse model systems. Biochem Cell Biol. 2009;87:117–25.PubMedCrossRef Shah S, Smith H, Feng X, Rancourt DE, Riabowol K. ING function in apoptosis in diverse model systems. Biochem Cell Biol. 2009;87:117–25.PubMedCrossRef
20.
Zurück zum Zitat Gunduz M, Gunduz E, Rivera RS, Nagatsuka H. The inhibitor of growth (ING) gene family: potential role in cancer therapy. Curr Cancer Drug Targets. 2008;8:275–84.PubMedCrossRef Gunduz M, Gunduz E, Rivera RS, Nagatsuka H. The inhibitor of growth (ING) gene family: potential role in cancer therapy. Curr Cancer Drug Targets. 2008;8:275–84.PubMedCrossRef
21.
Zurück zum Zitat Cheung Jr KJ, Li G. The tumor suppressor ING1: structure and function. Exp Cell Res. 2001;268:1–6.PubMedCrossRef Cheung Jr KJ, Li G. The tumor suppressor ING1: structure and function. Exp Cell Res. 2001;268:1–6.PubMedCrossRef
22.
Zurück zum Zitat Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature. 1999;402:672–6.PubMedCrossRef Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature. 1999;402:672–6.PubMedCrossRef
23.
Zurück zum Zitat Aita VM, Liang XH, Murty VV, Pincus DL, Yu W, Cayanis E, et al. Cloning and genomic organization of beclin 1, a candidate tumor suppressor gene on chromosome 17q21. Genomics. 1999;59:59–65.PubMedCrossRef Aita VM, Liang XH, Murty VV, Pincus DL, Yu W, Cayanis E, et al. Cloning and genomic organization of beclin 1, a candidate tumor suppressor gene on chromosome 17q21. Genomics. 1999;59:59–65.PubMedCrossRef
24.
Zurück zum Zitat Kihara A, Kabeya Y, Ohsumi Y, Yoshimori T. Beclin-phosphatidylinositol 3-kinase complex functions at the trans-Golgi network. EMBO Rep. 2001;2:330–5.PubMedCrossRef Kihara A, Kabeya Y, Ohsumi Y, Yoshimori T. Beclin-phosphatidylinositol 3-kinase complex functions at the trans-Golgi network. EMBO Rep. 2001;2:330–5.PubMedCrossRef
25.
Zurück zum Zitat Meschini S, Condello M, Lista P, Arancia G. Autophagy: molecular mechanisms and their implications for anticancer therapies. Curr Cancer Drug Targets. 2011;11:357–79.PubMedCrossRef Meschini S, Condello M, Lista P, Arancia G. Autophagy: molecular mechanisms and their implications for anticancer therapies. Curr Cancer Drug Targets. 2011;11:357–79.PubMedCrossRef
26.
Zurück zum Zitat Chen N, Karantza V. Autophagy as a therapeutic target in cancer. Cancer Biol Ther. 2011;11:157–68.PubMedCrossRef Chen N, Karantza V. Autophagy as a therapeutic target in cancer. Cancer Biol Ther. 2011;11:157–68.PubMedCrossRef
27.
Zurück zum Zitat Cheung Jr KJ, Mitchell D, Lin P, Li G. The tumor suppressor candidate p33(ING1) mediates repair of UV-damaged DNA. Cancer Res. 2001;61:4974–7.PubMed Cheung Jr KJ, Mitchell D, Lin P, Li G. The tumor suppressor candidate p33(ING1) mediates repair of UV-damaged DNA. Cancer Res. 2001;61:4974–7.PubMed
28.
Zurück zum Zitat Gong W, Suzuki K, Russell M, Riabowol K. Function of the ING family of PHD proteins in cancer. Int J Biochem Cell Biol. 2005;37:1054–65.PubMedCrossRef Gong W, Suzuki K, Russell M, Riabowol K. Function of the ING family of PHD proteins in cancer. Int J Biochem Cell Biol. 2005;37:1054–65.PubMedCrossRef
29.
Zurück zum Zitat Nouman GS, Anderson JJ, Lunec J, Angus B. The role of the tumour suppressor p33 ING1b in human neoplasia. J Clin Pathol. 2003;56:491–6.PubMedCrossRef Nouman GS, Anderson JJ, Lunec J, Angus B. The role of the tumour suppressor p33 ING1b in human neoplasia. J Clin Pathol. 2003;56:491–6.PubMedCrossRef
30.
Zurück zum Zitat Kameyama K, Huang CL, Liu D, Masuya D, Nakashima T, Sumitomo S, et al. Reduced ING1b gene expression plays an important role in carcinogenesis of non-small cell lung cancer patients. Clin Cancer Res. 2003;9:4926–34.PubMed Kameyama K, Huang CL, Liu D, Masuya D, Nakashima T, Sumitomo S, et al. Reduced ING1b gene expression plays an important role in carcinogenesis of non-small cell lung cancer patients. Clin Cancer Res. 2003;9:4926–34.PubMed
31.
Zurück zum Zitat Guo XB, Jing CQ, Li LP, Zhang L, Shi YL, Wang JS, et al. Down-regulation of miR-622 in gastric cancer promotes cellular invasion and tumor metastasis by targeting ING1 gene. World J Gastroenterol. 2011;17:1895–902.PubMed Guo XB, Jing CQ, Li LP, Zhang L, Shi YL, Wang JS, et al. Down-regulation of miR-622 in gastric cancer promotes cellular invasion and tumor metastasis by targeting ING1 gene. World J Gastroenterol. 2011;17:1895–902.PubMed
32.
Zurück zum Zitat Charoenkwan P, Senger C, Weitzman S, Sexsmith E, Sherman CG, Malkin D, et al. Significance of p53 expression in immature teratomas. Pediatr Dev Pathol. 2002;5:499–507.PubMedCrossRef Charoenkwan P, Senger C, Weitzman S, Sexsmith E, Sherman CG, Malkin D, et al. Significance of p53 expression in immature teratomas. Pediatr Dev Pathol. 2002;5:499–507.PubMedCrossRef
33.
Zurück zum Zitat Adorno M, Cordenonsi M, Montagner M, Dupont S, Wong C, Hann B, et al. A mutant-p53/Smad complex opposes p63 to empower TGFbeta-induced metastasis. Cell. 2009;137:87–98.PubMedCrossRef Adorno M, Cordenonsi M, Montagner M, Dupont S, Wong C, Hann B, et al. A mutant-p53/Smad complex opposes p63 to empower TGFbeta-induced metastasis. Cell. 2009;137:87–98.PubMedCrossRef
34.
Zurück zum Zitat Kogan-Sakin I, Tabach Y, Buganim Y, Molchadsky A, Solomon H, Madar S, et al. Mutant p53(R175H) upregulates Twist1 expression and promotes epithelial-mesenchymal transition in immortalized prostate cells. Cell Death Differ. 2011;18:271–81.PubMedCrossRef Kogan-Sakin I, Tabach Y, Buganim Y, Molchadsky A, Solomon H, Madar S, et al. Mutant p53(R175H) upregulates Twist1 expression and promotes epithelial-mesenchymal transition in immortalized prostate cells. Cell Death Differ. 2011;18:271–81.PubMedCrossRef
35.
Zurück zum Zitat Grander D, Panaretakis T. Autophagy: cancer therapy's friend or foe? Future Med Chem. 2010;2:285–97.PubMedCrossRef Grander D, Panaretakis T. Autophagy: cancer therapy's friend or foe? Future Med Chem. 2010;2:285–97.PubMedCrossRef
36.
37.
Zurück zum Zitat Shintani T, Klionsky DJ. Autophagy in health and disease: a double-edged sword. Science. 2004;306:990–5.PubMedCrossRef Shintani T, Klionsky DJ. Autophagy in health and disease: a double-edged sword. Science. 2004;306:990–5.PubMedCrossRef
38.
Zurück zum Zitat Chen N, Karantza-Wadsworth V. Role and regulation of autophagy in cancer. Biochim Biophys Acta. 2009;1793:1516–23.PubMedCrossRef Chen N, Karantza-Wadsworth V. Role and regulation of autophagy in cancer. Biochim Biophys Acta. 2009;1793:1516–23.PubMedCrossRef
39.
Zurück zum Zitat Won KY, Kim GY, Kim YW, Song JY, Lim SJ. Clinicopathologic correlation of beclin-1 and bcl-2 expression in human breast cancer. Hum Pathol. 2010;41:107–12.PubMedCrossRef Won KY, Kim GY, Kim YW, Song JY, Lim SJ. Clinicopathologic correlation of beclin-1 and bcl-2 expression in human breast cancer. Hum Pathol. 2010;41:107–12.PubMedCrossRef
Metadaten
Titel
The expression of p33ING1, p53, and autophagy-related gene Beclin1 in patients with non-small cell lung cancer
verfasst von
Jun Liu
Yongping Lin
Haihong Yang
Qiuhua Deng
Guoqin Chen
Jianxing He
Publikationsdatum
01.12.2011
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 6/2011
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-011-0211-4

Weitere Artikel der Ausgabe 6/2011

Tumor Biology 6/2011 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.