Abstract
To identify novel cellular genes that could potentially act as predictive molecular markers for human cervical cancer, we employed RT–PCR differential display, reverse Northern and Northern blot analysis to compare the gene expression profiles between squamous cell carcinoma biopsies and adjacent histo-pathological normal epithelium tissues. Twenty-eight cDNA clones were isolated that were demonstrated to be consistently over-expressed in squamous cell cervical cancer biopsies of FIGO stages 1B to 3B. Most importantly, it was observed that, in addition to their over-expression in cancer lesions, some of these genes are upregulated in the presumably histo-pathological normal adjacent tissues. Of particular interest is clone G30CC that has been identified to be the gene that encodes S12 ribosomal protein. When employed for RNA–RNA in situ hybridization experiments, expression of G30CC could be detected in the immature basal epithelial cells of histo-pathological normal tissues collected from cervical cancer patients of early FIGO stages. In comparison, the expression of G30CC was not detected in cervical tissues collected from patients admitted for surgery of non-malignant conditions. These results allow the distinct possibility of employing the ribosomal protein S12 gene as an early molecular diagnostic identifier for the screening of human cervical cancer and a potential target employed for cancer gene therapy trials.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 24 print issues and online access
$259.00 per year
only $10.79 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Basset P, Bellocq JP, Wolf C, Stoll I, Hutin P, Limacher JM, Podhajcer OL, Chenard MP, Rio MC, Chambon P (1990) A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas. Nature 348: 699–704
Bos AB, van Ballegooijen M, van Oortmarssen GJ, van Marle ME, Habbema JD, Lynge E (1997) Non-progression of cervical intraepithelial neoplasia estimated from population-screening data. Br J Cancer 75: 124–130
Bosch FX, Manos MM, Munoz N, Sherman M, Jansen AM, Peto J, Schiffman MH, Moreno V, Kurman R, Shah KV (1995) Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. J Natl Cancer Inst 87: 796–802
Burke TW, Hoskins WJ, Heller PB, Shen MC, Weiser EB, Park RC (1987) Clinical patterns of tumor recurrence after radical hysterectomy in stage IB cervical carcinoma. Obstet Gynecol 69: 382–385
Chanseob S, Zhang W, Chang HR, Lee JH (1998) Profiling of differentially expressed genes in human primary cervical cancer by complementary DNA expression array. Clin Cancer Res 4: 3045–3050
Chiquet-Ehrismann R, Mackie EJ, Pearson CA, Sakakura T (1986) Tenascin: an extracellular matrix protein involved in tissue interactions during fetal development and oncogenesis. Cell 47: 131–139
Duggan MA, McGregor SE, Stuart GC, Morris S, Chang-Poon V, Schepansky A, Honore L (1998) The natural history of CIN I lesions. Eur J Gynaecol Oncol 19: 338–344
Ellis MJ, Singer C, Hornby A, Rasmussen A, Cullen KJ (1994) Insulin-like growth factor mediated stromal-epithelial interactions in human breast cancer. Breast Cancer Res Treat 31: 249–261
Erikson E, Maller JL (1989) In vivo phosphorylation and activation of ribosomal protein S6 kinases during Xenopus oocyte maturation. J Biol Chem 264: 13711–13717
FIGO News (1987) Int J Gynaecol Obstet 25: 87
Frazier KS, Grotendorst GR (1997) Expression of connective tissue growth factor mRNA in the fibrous stroma of mammary tumors. Int J Biochem Cell Biol 29: 153–161
Hartwell LH, Kastan MB (1994) Cell cycle control and cancer. Science 266: 1821–1828
Henry JL, Coggin DL, King CR (1993) High-level expression of the ribosomal protein L19 in human breast tumors that overexpress erbB-2. Cancer Res 53: 1403–1408
Herrero R, Hildesheim A, Bratti C, Sherman ME, Hutchinson M, Morales J, Balmaceda I, Greenberg MD, Alfaro M, Burk RD, Wacholder S, Plummer M, Schiffman M (2000) Population-based study of human papillomavirus infection and cervical neoplasia in rural Costa Rica. J Natl Cancer Inst 92: 464–474
Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD (1998) Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med 338: 423–428
Kjaer SK, van den Brule AJ, Bock JE, Poll PA, Engholm G, Sherman ME, Walboomers JM, Meijer CJ (1997) Determinants for genital human papillomavirus (HPV) infection in 1000 randomly chosen young Danish women with normal Pap smear: are there different risk profiles for oncogenic and nononcogenic HPV types? Cancer Epidemiol Biomark Prev 6: 799–805
Klaes R, Woerner SM, Ridder R, Wentzensen N, Duerst M, Schneider A, Lotz B, Melsheimer P, von Knebel Doeberitz M (1999) Detection of high-risk cervical intraepithelial neoplasia and cervical cancer by amplification of transcripts derived from integrated papillomavirus oncogenes. Cancer Res 59: 6132–6136
Kumar KU, Srivastava SP, Kaufman RJ (1999) Double-stranded RNA-activated protein kinase (PKR) is negatively regulated by 60S ribosomal subunit protein L18. Mol Cell Biol 19: 1116–1125
Lanciano R (1996) Radiotherapy for the treatment of locally recurrent cervical cancer. J Natl Cancer Inst Monogr 21: 113–115
Liang P, Pardee AB (1992) Differential display of eukaryotic RNA by means of the polymerase chain reaction. Science 257: 967–970
Liang P, Averboukh L, Pardee AB (1993) Distribution and cloning of eukaryotic mRNAs by means of differential display: refinements and optimization. Nucleic Acids Res 21: 3269–3275
Liang P, Zhu W, Zhang X, Guo Z, O'Connell RP, Averboukh L, Wang F, Pardee AB (1994) Differential display using one-base anchored oligo-dT primers. Nucleic Acids Res 22: 5763–5764
Nakamura T, Matsumoto K, Kiritoshi A, Tano Y, Nakamura T (1997) Induction of hepatocyte growth factor in fibroblasts by tumor-derived factors affects invasive growth of tumor cells: in vitro analysis of tumor-stromal interactions. Cancer Res 57: 3305–3313
Olumi AF, Grossfeld GD, Hayward SW, Carroll PR, Tlsty TD, Cunha GR (1999) Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res 59: 5002–5011
Ostor AG (1993) Natural history of cervical intraepithelial neoplasia: a critical review. Int J Gynecol Pathol 12: 186–192
Piamsomboon S, Termrungruanglert W, Kudelka AP, Edwards CL, Freedman RS, Mountain CF, Delclos L, Aapro MS, DeCaro L, Bianca J, Verschraegen CF, Kavanagh JJ (1996) Prolonged stabilization of progressive squamous cell cancer of the cervix with interferon-alpha and 13-cis-retinoic acid: report of two cases and review of the literature. Anticancer Drugs 7: 800–804
Pogue-Geile K, Geiser JR, Shu M, Miller C, Wool IG, Meisler AI, Pipas JM (1991) Ribosomal protein genes are overexpressed in colorectal cancer: isolation of a cDNA clone encoding the human S3 ribosomal protein. Mol Cell Biol 11: 3842–3849
Rinehart CA, Torti VR (1997) Aging and cancer: the role of stromal interactions with epithelial cells. Mol Carcinog 18: 187–192
Ronco LV, Karpova AY, Vidal M, Howley PM (1998) Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity. Genes Dev 12: 2061–2072
Ronnov-Jessen L, Petersen OW, Bissell MJ (1996) Cellular changes involved in conversion of normal to malignant breast: importance of the stromal reaction. . Physiol Rev 76: 69–125
Singer C, Rasmussen A, Smith HS, Lippman ME, Lynch HT, Cullen KJ (1995) Malignant breast epithelium selects for insulin-like growth factor II expression in breast stroma: evidence for paracrine function. Cancer Res 55: 2448–2454
Skobe M, Fusenig NE (1998) Tumorigenic conversion of immortal human keratinocytes through stromal cell activation. Proc Natl Acad Sci 95: 1050–1055
Soong TW, Hui KM (1992) Locus-specific transcriptional control of HLA genes. J Immunol 149: 2008–2020
Tlsty TD, Hein PW (2001) Know thy neighbor: stromal cells can contribute oncogenic signals. Curr Opin Genet Dev 11: 54–59
Vizcaino AP, Moreno V, Bosch FX, Munoz N, Barros-Dios XM, Borras J, Parkin DM (2000) International trends in incidence of cervical cancer: II. Squamous cell carcinoma. Int J Cancer 86: 429–435
Weinberg RA (1996) How cancer arises. Sci Am 275: 62–70
Wright JH, McDonnell S, Portella G, Bowden GT, Balmain A, Matrisian LM (1994) A switch from stromal to tumor cell expression of stromelysin-1 mRNA associated with the conversion of squamous to spindle carcinomas during mouse skin tumor progression. Mol Carcinog 10: 207–215
Yan G, Fukabori Y, McBride G, Nikolaropolous S, McKeehan WL (1993) Exon switching and activation of stromal and embryonic fibroblast growth factor (FGF)-FGF receptor genes in prostate epithelial cells accompany stromal independence and malignancy. Mol Cell Biol 13: 4513–4522
Yee D, Rosen N, Favoni RE, Cullen KJ (1991) The insulin-like growth factors, their receptors, and their binding proteins in human breast cancer. Cancer Treat Res 53: 93–106
Ziemiecki A, Muller RG, Fu XC, Hynes NE, Kozma S (1990) Oncogenic activation of the human trk proto-oncogene by recombination with the large ribosomal subunit protein L7a. EMBO J 9: 191–195
zur Hausen H (2000) Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis. J Natl Cancer Inst 92: 690–698
Acknowledgements
This study was supported by the Singapore National Medical Research Council and the Singapore National Science and Technology Board.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Cheng, Q., Lau, W., Chew, S. et al. Identification of molecular markers for the early detection of human squamous cell carcinoma of the uterine cervix. Br J Cancer 86, 274–281 (2002). https://doi.org/10.1038/sj.bjc.6600038
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bjc.6600038
Keywords
This article is cited by
-
Analysis of PPI networks of transcriptomic expression identifies hub genes associated with Newcastle disease virus persistent infection in bladder cancer
Scientific Reports (2023)
-
HumanaFly: high-throughput transgenesis and expression of breast cancer transcripts in Drosophila eye discovers the RPS12-Wingless signaling axis
Scientific Reports (2020)
-
Overexpression, purification, molecular characterization and the effect on tumor growth of ribosomal protein L22 from the Giant Panda (Ailuropoda melanoleuca)
Molecular Biology Reports (2014)
-
Expression, purification, and evaluation for anticancer activity of ribosomal protein L31 gene (RPL31) from the giant panda (Ailuropoda melanoleuca)
Molecular Biology Reports (2012)
-
MYC as a regulator of ribosome biogenesis and protein synthesis
Nature Reviews Cancer (2010)