Abstract
Cyclin Dependent Kinase 4 (Cdk4) is known to be an oncogene and is involved in various cancers. It is overexpressed either by genomic amplification or by c-myc dependent manner. Our preliminary results indicate high expression of protein and mRNA as well as absence of genomic amplification in early oral cancer development. One transcription factor (TF) binding site has been detected from −281 to −298 by using DNase I foot printing and confirmed by electrophoretic mobility shift assay. This is a novel DNA sequence. The recruitment of this new TF as well as the earlier reported c-myc was analyzed in various stage of oral cancer development. The binding activity of the new TF is present in normal tissues and observed more in initial stage samples whereas c-myc expression was absent in normal and more in higher stage of oral cancer development. On the basis of these findings we propose the new TF to be a possible CdK4 Regulating Factor (KRF). This might maintain the basal level transcription in normal and activates Cdk4 transcription in the initial stage, where as the same role is carried by c-myc in higher stage of chewing tobacco mediated oral cancer development.
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Pisani P, Parkin DM, Bray F & Ferlay J (1999) Int. J. Cancer 83(6): 870–873
Sen U, Sankarnarayan R, Mandal S, Ramana Kumar AV, Parkin DM & Siddig M (2002) Int. J. Cancer 100(1): 86–91
Tam SW, Theodoras AM, Shay JW, Draetta GF & Pagano M (1994) Oncogene 9: 2663–2674
Kato J, Matsushime H, Heibert SW, Ewen ME & Sherr CJ (1993) Genes Dev. 7(3): 331–342
Meyerson M & Harlow E (1994) Mol Cell Biol. 14(3): 2077–2086
Koontongkaew S, Chareonkitkajorn L, Chanvitan A, Leelakriangsak M & Amornphimoltham P (2000) Oral Oncol. 36(4): 334–339
Patel V, Jakus J, Harris CM, Ensley JF, Robbins KC & Yeudall WA (1997) Int. J. Cancer 73(4): 551–555
Owonikoko T, Loberg C, Gabbert HE & Sabia M (2001) J. Pathol. 193(2): 155–161
Dang Y, Sui L, Sujimoto K, Tai Y & Tokuda M (2001) Int. J. Cancer 95: 209–215
Masciullo V, Scambia G, Marone M, Giannitelli C, Ferrandina G, Bellacosa A, Benedetti PP & Mancuso S (1997) Int. J. Cancer 74(4): 390–395
Reed SI (1992) Annu. Rev. Cell Biol. 8: 529–561
Matsushime H, Quelle DE, Shurtleff SA, Shihuya M, Sherr CJ & Kato JY (1994) Mol Cell Biol. 14(3): 2066–2076
Haas S, Bosch FX, Klein-Kuhne W, Nollert J, Rudat V & Conradt C (1999) HNO 47: 777–786
An HX, Beckmann MW, Reifenberger G, Bender HG & Niederacher D (1999) Am. J. Pathol. 154(1): 113–118
Reifenberger G, Reifenberger J, Ichimura K, Meltzer PS & Collin VP (1994) Cancer Res. 54(16): 4299–4203
Wunder JS, Eppert K, Burrow SR, Gogkoz N, Bell RS & Andrulis IL (1999) Oncogene 18: 783–788
Hermeking H, Rago C, Schuhmacher M, Li Q, Barrett JF, Obaya AJ, O'Connell BC, Mateyak MK, Tam W, Kohlhuber F, Dang CV, Sedivy JM, Eick D, Vogelstein B & Kinzler KW (2000) Pros. Nat. Acad. Sci. 97(5): 2229–2234
Mateyak MK, Obaya AJ & Sedivy JM (1999) Mol. Cell. Biol. 19(7): 4672–4683
Ewen ME, Sluss HK, Whitehouse LL & Livingston DM (1993) Cell 74(6): 1009–1020
Miller SJ, Suthiphongchai T, Zambetti GP & Ewen ME (2000) Mol Cell Biol. 20(22): 8420–8431
Patnaik S, Nayak BK & Das BR (1999) IUBMB Life 48(3): 305–309
Baral R, Patnaik S & Das BR (1998) Eur. J. Oral. Sci. 106(5): 907–913
Sambrook J, Fritsch EF & Maniatis T (1989) Molecular cloning - a laboratory manual 2nd ed.,Cold Spring Harbour Laboratory Press
Nagpal JK, Mishra R & Das BR (2002) Cancer 94(9): 2393–2400
Hattori M, Tugores A, Veloz L, Karin M & Brenner DA (1990) DNA Cell Biol. 9(10): 777–781
Zaret KS, Liu JK & Dipersio CM (1990) Pros. Natl. Acad. Sci. 87(14): 5469–5473
Briggs MR, Kadonaga JT, Bell SP & Tjian R (1986) Science 234(4772): 47–52
Lucas J, Parry D, Aagaard L, Mann DJ, Bartkova J, Strauss M Peters G & Bartek J (1995) Nature 375(6531): 503–506
Weinberg RA (1995) Cell 81(3): 323–330
Nobori T, Miura K, Wu DJ, Lois A, Takabayashi K & Carson DA (1994) Nature 368(6473): 753–756
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Mishra, R., Ranjan Das, B. Early overexpression of Cdk4 and possible role of KRF and c-myc in chewing tobacco mediated oral cancer development. Mol Biol Rep 30, 207–213 (2003). https://doi.org/10.1023/A:1026384402585
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DOI: https://doi.org/10.1023/A:1026384402585