Top

Molecular Cancer

Published in:

Open Access 01-12-2005 | Research

Tumor suppressor in lung cancer 1 (TSLC1) alters tumorigenic growth properties and gene expression

Authors: Thomas E Sussan, Mathew T Pletcher, Yoshinori Murakami, Roger H Reeves

Published in: Molecular Cancer | Issue 1/2005

Abstract

Background

Introduction of cDNA or genomic clones of the tumor suppressor in lung cancer 1 (TSLC1) gene into the non-small cell lung cancer line, A549, reverses tumorigenic growth properties of these cells. These results and the observation that TSLC1 is down-regulated in a number of tumors suggest that TSLC1 functions as a critical switch mediating repression of tumorigenesis.

Results

To investigate this mechanism, we compared growth properties of A549 with the TSLC1-containing derivative. We found a G1/S phase transition delay in 12.2. Subtractive hybridization, quantitative PCR, and TranSignal Protein/DNA arrays were used to identify genes whose expression changed when TSLC1 was up-regulated. Members of common G1/S phase regulatory pathways such as TP53, MYC, RB1 and HRAS were not differentially expressed, indicating that TSLC1 may function through an alternative pathway(s). A number of genes involved in cell proliferation and tumorigenesis were differentially expressed, notably genes in the Ras-induced senescence pathway. We examined expression of several of these key genes in human tumors and normal lung tissue, and found similar changes in expression, validating the physiological relevance of the A549 and 12.2 cell lines.

Conclusion

Gene expression and cell cycle differences provide insights into potential downstream pathways of TSLC1 that mediate the suppression of tumor properties in A549 cells.

Available only for authorised users

Ihde DC, Minna JD: Non-small cell lung cancer. Part I: Biology, diagnosis, and staging. Curr Probl Cancer. 1991, 15: 61-104.PubMed

Suzuki Y, Orita M, Shiraishi M, Hayashi K, Sekiya T: Detection of ras gene mutations in human lung cancers by single-strand conformation polymorphism analysis of polymerase chain reaction products. Oncogene. 1990, 5: 1037-1043.PubMed

Birrer MJ, Minna JD: Genetic changes in the pathogenesis of lung cancer. Annu Rev Med. 1989, 40: 305-317. 10.1146/annurev.me.40.020189.001513CrossRefPubMed

Kishimoto Y, Murakami Y, Shiraishi M, Hayashi K, Sekiya T: Aberrations of the p53 tumor suppressor gene in human non-small cell carcinomas of the lung. Cancer Res. 1992, 52: 4799-4804.PubMed

Sachse R, Murakami Y, Shiraishi M, Hayashi K, Sekiya T: DNA aberrations at the retinoblastoma gene locus in human squamous cell carcinomas of the lung. Oncogene. 1994, 9: 39-47.PubMed

Wang SS, Esplin ED, Li JL, Huang L, Gazdar A, Minna J, Evans GA: Alterations of the PPP2R1B gene in human lung and colon cancer. Science. 1998, 282: 284-287. 10.1126/science.282.5387.284CrossRefPubMed

Kuramochi M, Fukuhara H, Nobukuni T, Kanbe T, Maruyama T, Ghosh HP, Pletcher M, Isomura M, Onizuka M, Kitamura T, Sekiya T, Reeves RH, Murakami Y: TSLC1 is a tumor-suppressor gene in human non-small-cell lung cancer. Nat Genet. 2001, 27: 427-430. 10.1038/86934CrossRefPubMed

Murakami Y, Nobukuni T, Tamura K, Maruyama T, Sekiya T, Arai Y, Gomyou H, Tanigami A, Ohki M, Cabin D, Frischmeyer P, Hunt P, Reeves RH: Localization of tumor suppressor activity important in nonsmall cell lung carcinoma on chromosome 11q. Proc Natl Acad Sci U S A. 1998, 95: 8153-8158. 10.1073/pnas.95.14.8153PubMedCentralCrossRefPubMed

Allinen M, Peri L, Kujala S, Lahti-Domenici J, Outila K, Karppinen SM, Launonen V, Winqvist R: Analysis of 11q21-24 loss of heterozygosity candidate target genes in breast cancer: indications of TSLC1 promoter hypermethylation. Genes Chromosomes Cancer. 2002, 34: 384-389. 10.1002/gcc.10079CrossRefPubMed

10.

Fukuhara H, Kuramochi M, Fukami T, Kasahara K, Furuhata M, Nobukuni T, Maruyama T, Isogai K, Sekiya T, Shuin T, Kitamura T, Reeves RH, Murakami Y: Promoter Methylation of TSLC1 and Tumor Suppression by Its Gene Product in Human Prostate Cancer. Jpn J Cancer Res. 2002, 93: 605-609.CrossRefPubMed

11.

Hui AB, Lo KW, Kwong J, Lam EC, Chan SY, Chow LS, Chan AS, Teo PM, Huang DP: Epigenetic inactivation of TSLC1 gene in nasopharyngeal carcinoma. Mol Carcinog. 2003, 38: 170-178. 10.1002/mc.10156CrossRefPubMed

12.

Honda T, Tamura G, Waki T, Jin Z, Sato K, Motoyama T, Kawata S, Kimura W, Nishizuka S, Murakami Y: Hypermethylation of the TSLC1 gene promoter in primary gastric cancers and gastric cancer cell lines. Jpn J Cancer Res. 2002, 93: 857-860.CrossRefPubMed

13.

Steenbergen RD, Kramer D, Braakhuis BJ, Stern PL, Verheijen RH, Meijer CJ, Snijders PJ: TSLC1 gene silencing in cervical cancer cell lines and cervical neoplasia. J Natl Cancer Inst. 2004, 96: 294-305.CrossRefPubMed

14.

Fukami T, Fukuhara H, Kuramochi M, Maruyama T, Isogai K, Sakamoto M, Takamoto S, Murakami Y: Promoter methylation of the TSLC1 gene in advanced lung tumors and various cancer cell lines. Int J Cancer. 2003, 107: 53-59. 10.1002/ijc.11348CrossRefPubMed

15.

Masuda M, Yageta M, Fukuhara H, Kuramochi M, Maruyama T, Nomoto A, Murakami Y: The tumor suppressor protein TSLC1 is involved in cell-cell adhesion. J Biol Chem. 2002, 277: 31014-31019. 10.1074/jbc.M203620200CrossRefPubMed

16.

Shingai T, Ikeda W, Kakunaga S, Morimoto K, Takekuni K, Itoh S, Satoh K, Takeuchi M, Imai T, Monden M, Takai Y: Implications of nectin-like molecule 2/IGSF4/RA175/SgIGSF/TSLC1/SynCAM1 in cell-cell adhesion and transmembrane protein localization in epithelial cells. J Biol Chem. 2003.

17.

Mao X, Seidlitz E, Ghosh K, Murakami Y, Ghosh HP: The cytoplasmic domain is critical to the tumor suppressor activity of TSLC1 in non-small cell lung cancer. Cancer Res. 2003, 63: 7979-7985.PubMed

18.

Yageta M, Kuramochi M, Masuda M, Fukami T, Fukuhara H, Maruyama T, Shibuya M, Murakami Y: Direct association of TSLC1 and DAL-1, two distinct tumor suppressor proteins in lung cancer. Cancer Res. 2002, 62: 5129-5133.PubMed

19.

Gomyo H, Arai Y, Tanigami A, Murakami Y, Hattori M, Hosoda F, Arai K, Aikawa Y, Tsuda H, Hirohashi S, Asakawa S, Shimizu N, Soeda E, Sakaki Y, Ohki M: A 2-Mb sequence-ready contig map and a novel immunoglobulin superfamily gene IGSF4 in the LOH region of chromosome 11q23.2. Genomics. 1999, 62: 139-146. 10.1006/geno.1999.6001CrossRefPubMed

20.

Biederer T, Sara Y, Mozhayeva M, Atasoy D, Liu X, Kavalali ET, Sudhof TC: SynCAM, a synaptic adhesion molecule that drives synapse assembly. Science. 2002, 297: 1525-1531. 10.1126/science.1072356CrossRefPubMed

21.

Wakayama T, Ohashi K, Mizuno K, Iseki S: Cloning and characterization of a novel mouse immunoglobulin superfamily gene expressed in early spermatogenic cells. Mol Reprod Dev. 2001, 60: 158-164. 10.1002/mrd.1072CrossRefPubMed

22.

Urase K, Soyama A, Fujita E, Momoi T: Expression of RA175 mRNA, a new member of the immunoglobulin superfamily, in developing mouse brain. Neuroreport. 2001, 12: 3217-3221. 10.1097/00001756-200110290-00015CrossRefPubMed

23.

Niklinski J, Niklinska W, Laudanski J, Chyczewska E, Chyczewski L: Prognostic molecular markers in non-small cell lung cancer. Lung Cancer. 2001, 34 Suppl 2: S53-8. 10.1016/S0169-5002(01)00345-2CrossRefPubMed

24.

Hirai K, Shimada H, Ogawa T, Taji S: The spread of human lung cancer cells on collagens and its inhibition by type III collagen. Clin Exp Metastasis. 1991, 9: 517-527. 10.1007/BF01768580CrossRefPubMed

25.

Ito T, Shimada Y, Hashimoto Y, Kaganoi J, Kan T, Watanabe G, Murakami Y, Imamura M: Involvement of TSLC1 in progression of esophageal squamous cell carcinoma. Cancer Res. 2003, 63: 6320-6326.PubMed

26.

Dvorak HF: Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol. 2002, 20: 4368-4380. 10.1200/JCO.2002.10.088CrossRefPubMed

27.

Kok K, Naylor SL, Buys CH: Deletions of the short arm of chromosome 3 in solid tumors and the search for suppressor genes. Adv Cancer Res. 1997, 71: 27-92.CrossRefPubMed

28.

Yang Y, Kiss H, Kost-Alimova M, Kedra D, Fransson I, Seroussi E, Li J, Szeles A, Kholodnyuk I, Imreh MP, Fodor K, Hadlaczky G, Klein G, Dumanski JP, Imreh S: A 1-Mb PAC contig spanning the common eliminated region 1 (CER1) in microcell hybrid-derived SCID tumors. Genomics. 1999, 62: 147-155. 10.1006/geno.1999.5952CrossRefPubMed

29.

Barradas M, Gonos ES, Zebedee Z, Kolettas E, Petropoulou C, Delgado MD, Leon J, Hara E, Serrano M: Identification of a candidate tumor-suppressor gene specifically activated during Ras-induced senescence. Exp Cell Res. 2002, 273: 127-137. 10.1006/excr.2001.5434CrossRefPubMed

30.

Mousses S, Bubendorf L, Wagner U, Hostetter G, Kononen J, Cornelison R, Goldberger N, Elkahloun AG, Willi N, Koivisto P, Ferhle W, Raffeld M, Sauter G, Kallioniemi OP: Clinical validation of candidate genes associated with prostate cancer progression in the CWR22 model system using tissue microarrays. Cancer Res. 2002, 62: 1256-1260.PubMed

31.

Guerreiro Da Silva ID, Hu YF, Russo IH, Ao X, Salicioni AM, Yang X, Russo J: S100P calcium-binding protein overexpression is associated with immortalization of human breast epithelial cells in vitro and early stages of breast cancer development in vivo. Int J Oncol. 2000, 16: 231-240.PubMed

32.

Beer DG, Kardia SL, Huang CC, Giordano TJ, Levin AM, Misek DE, Lin L, Chen G, Gharib TG, Thomas DG, Lizyness ML, Kuick R, Hayasaka S, Taylor JM, Iannettoni MD, Orringer MB, Hanash S: Gene-expression profiles predict survival of patients with lung adenocarcinoma. Nat Med. 2002, 8: 816-824.PubMed

33.

Brandt B, Roetger A, Bidart JM, Packeisen J, Schier K, Mikesch JH, Kemming D, Boecker W, Yu D, Buerger H: Early placenta insulin-like growth factor (pro-EPIL) is overexpressed and secreted by c-erbB-2-positive cells with high invasion potential. Cancer Res. 2002, 62: 1020-1024.PubMed

34.

Pishvaian MJ, Feltes CM, Thompson P, Bussemakers MJ, Schalken JA, Byers SW: Cadherin-11 is expressed in invasive breast cancer cell lines. Cancer Res. 1999, 59: 947-952.PubMed

35.

Feltes CM, Kudo A, Blaschuk O, Byers SW: An alternatively spliced cadherin-11 enhances human breast cancer cell invasion. Cancer Res. 2002, 62: 6688-6697.PubMed

36.

Shibata T, Ochiai A, Kanai Y, Akimoto S, Gotoh M, Yasui N, Machinami R, Hirohashi S: Dominant negative inhibition of the association between beta-catenin and c-erbB-2 by N-terminally deleted beta-catenin suppresses the invasion and metastasis of cancer cells. Oncogene. 1996, 13: 883-889.PubMed

37.

Retera JM, Leers MP, Sulzer MA, Theunissen PH: The expression of beta-catenin in non-small-cell lung cancer: a clinicopathological study. J Clin Pathol. 1998, 51: 891-894.PubMedCentralCrossRefPubMed

38.

Mao X, Seidlitz E, Truant R, Hitt M, Ghosh HP: Re-expression of TSLC1 in a non-small-cell lung cancer cell line induces apoptosis and inhibits tumor growth. Oncogene. 2004, 23: 5632-5642. 10.1038/sj.onc.1207756CrossRefPubMed

39.

Feinberg AP, Vogelstein B: A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983, 132: 6-13. 10.1016/0003-2697(83)90418-9CrossRefPubMed

40.

Schwartz DC, Cantor CR: Separation of yeast chromosome-sized DNAs by pulsed field gradient gel electrophoresis. Cell. 1984, 37: 67-75. 10.1016/0092-8674(84)90301-5CrossRefPubMed

41.

Liu HC, Mele C, Catz D, Noyes N, Rosenwaks Z: Production of insulin-like growth factor binding proteins (IGFBPs) by human endometrial stromal cell is stimulated by the presence of embryos. J Assist Reprod Genet. 1995, 12: 78-87.CrossRefPubMed

42.

Tarrade A, Rochette-Egly C, Guibourdenche J, Evain-Brion D: The expression of nuclear retinoid receptors in human implantation. Placenta. 2000, 21: 703-710. 10.1053/plac.2000.0568CrossRefPubMed

43.

Kao LC, Tulac S, Lobo S, Imani B, Yang JP, Germeyer A, Osteen K, Taylor RN, Lessey BA, Giudice LC: Global gene profiling in human endometrium during the window of implantation. Endocrinology. 2002, 143: 2119-2138. 10.1210/en.143.6.2119CrossRefPubMed

44.

Chen GT, Getsios S, MacCalman CD: Cadherin-11 is a hormonally regulated cellular marker of decidualization in human endometrial stromal cells. Mol Reprod Dev. 1999, 52: 158-165. 10.1002/(SICI)1098-2795(199902)52:2<158::AID-MRD6>3.0.CO;2-3CrossRefPubMed

45.

Tsai SJ, Wu MH, Chen HM, Chuang PC, Wing LY: Fibroblast growth factor-9 is an endometrial stromal growth factor. Endocrinology. 2002, 143: 2715-2721. 10.1210/en.143.7.2715CrossRefPubMed

46.

Mock P, Frydman R, Bellet D, Diawara DA, Lavaissiere L, Troalen F, Bidart JM: Pro-EPIL forms are present in amniotic fluid and maternal serum during normal pregnancy. J Clin Endocrinol Metab. 1999, 84: 2253-2256. 10.1210/jc.84.6.2253CrossRefPubMed

47.

Morrish DW, Linetsky E, Bhardwaj D, Li H, Dakour J, Marsh RG, Paterson MC, Godbout R: Identification by subtractive hybridization of a spectrum of novel and unexpected genes associated with in vitro differentiation of human cytotrophoblast cells. Placenta. 1996, 17: 431-441. 10.1016/S0143-4004(96)90025-9CrossRefPubMed

Title: Tumor suppressor in lung cancer 1 (TSLC1) alters tumorigenic growth properties and gene expression
Authors: Thomas E Sussan
Mathew T Pletcher
Yoshinori Murakami
Roger H Reeves
Publication date: 01-12-2005
Publisher: BioMed Central
Published in: Molecular Cancer / Issue 1/2005
Electronic ISSN: 1476-4598
DOI: https://doi.org/10.1186/1476-4598-4-28

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2005

Overcoming cisplatin resistance by mTOR inhibitor in lung cancer

Amplification and overexpression of the ID4 gene at 6p22.3 in bladder cancer

Metallothionien 3 expression is frequently down-regulated in oesophageal squamous cell carcinoma by DNA methylation

Molecular and cytological features of the mouse B-cell lymphoma line iMycEμ-1

Reduced expression of multiple gap junction proteins is a feature of cervical dysplasia

Enhanced levels of Hsulf-1 interfere with heparin-binding growth factor signaling in pancreatic cancer

Keynote webinar | Spotlight on antibody–drug conjugates in cancer