(cell (vitronectin) CD (E CD, N CD, P CD ) R GD (

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1 Carcinogenesis T eratogenesis and M utagenesis V o l 8 N o , R GD R GD S (S: ), (ex tracellu lar m atrix ECM ),, 1., Α Β, (3) 1. 2 (cell adhesion m o lecu lar CAM ) : ( In2, tegrin) (lam recep to r) 65KD a B (Cadherin) CD 44 (4), 1. 1, ECM (1), Α ( 14 ) Β ( 8 ) 1. 3 ( 20 ) (Cadherin CD ) ECM (5) (fib ronectin) (vitronectin) CD (ECD, N CD, PCD ) R GD ( : ), (1, 2),,, : R GD ECD, 233

2 ECD PCR ECD m RNA ECD m RNA ECD, 9 ECD, CD 44v,, ;, ECD CD 44v, D ukers (10) R T PCR ECD cdna, CD 44 (11) (6) ECD CD 44v6,, CD 44v6 D ukers 1. 4CD 44 CD 44 CD (7) CD 44,, :,,,, :, 1 ; 2 ; 3 CD 44 11, 20 ; 4, kb (8) CD 44 V (tpa ) (upa ) CD 44 CD 44 (CD 44s), V CD 44 upa upa CD 44 (CD 44v)V 12, upa upa upa V PA I1, (12) upa, (13) CD 44s 162 PA I1, upa CD 44v, upa (9), BSP73A SM L CD 44s upa upa CD 44v, CD 44v CD 44s, 10 CD 44cDNA 2. 2 Ca + +, BSP73A S, Zn CD 44s CD 44v; (m a2

3 trix m etallop ro teinases MM P ) : EGFR, MM P1 ( ) MM P2 (g ) , V EGF, V EGF (T IM P)T IM P1 T IM P2 g MM P2 TN P470 (14) MM P T IM P (15) MM P T IM P 4. T GFΒ 4. 1 C (PKC), 2. 3B PKC g L ew is B 16 PKC CB, CB, g 10 g (16) EL ISA PKC ΑΒg g Χ Ε n CB CL, CL (L ) Η Ν Κ (21) PKC (17) 2. 4, Βm RNA (22) ph PKC D, PKCn (L ), PKC ras, fo s, c- m et,, 50%, 510, ( scatter facto r ) 70% (EGF) 10% c- m et, (PD GF) Α(T GFΑ) (20) TN P470 bfgf (Cathep sin B, CB ) H (CH ) L (CL ),,, PKC (L )m RNA, PKC- Βm RNA (23), 8g9 c- m et (bfgf), c - m et (V EGF) (24) c- erbb 2 H ER 2gneu, neu N o rthern EGFR bfgf (18), D uk2 EGF (EGFR ) ers D D ukers A - C (19) EGFR, 235

4 (25) P53 P53 39%, P53 (26) M T SgP16 (M u ltip le T um o r Supp resso r gene 1), 4 (CD K4), 4. 3, H 2K (1) ; ,,, T IM P,, nm 23 nm 23 H au t nm 23 (27) Yam ayuch i 21 nm 23,,,, nm 23 (28) nm 23 (29) nm 23 (30),,,, 1. H ynes Ro. Integrins: V ersatility, modulation and signal2 ing in cell adhesion. Cell, 1992; 29 (1) : H umph ries M J, O lden K, Yam ada KM. A synthetic pep2 tide from fibronectin inhibits experim ental m etastasis of m urine m elanom a cell. S cience, 1986; 233 (2) : Ko retz K. Exp ression of Α2, Α6, Β1chains in no rm alm uco sa and in adenom as of the co lon, co lon carcinom a and their liver m etastasis. A m er J P athol, 1991; 139 ( 3): 741 -, Rao C, Castronovo V, Schm itt M C, et al. Evidence fo r a p recurso r of the high - affinity m etastasis associated m urine lam inin recepo ṙ B iochem istry, 1989; 28: Takeichi M. Cadherins: a mo lecular fam ily impo rtant in selective cell- cell adhesion. A nnu R ev B iochem, 1990; Fyixen U H, Beh rens J, Sach sm, et al. E- cadherin m edi2 ated in cell- cell adherin p revents invasions of hum an co lo rectal carcinom as cell. J Cell B iol, 1991; 116 (1) : Tod A B row n, Tocld Bouchard, Tom ST, et al. H um an kerationocytes exp ression a new CD 44 co re p ro tein (CD 44E) as a heparan sulfate intrinsic m em brane p ro2 teaglycan. J Cell B iol, 1991; 113 (1) : Screaton, GR, Bell M V, D avid G, et al. Genom ic struc2 ture of DNA encoding the lymphocytes hom eing recepo r CD 44 reveals at least 12 alternatively sp liced exons. P roc N atl A cad S ci U SA, 1992; 89 (23) : Gunthert U, Hofm ann M, Rudy W, et al. A new variant of glyop ro tein CD 44 confers m etastatic po tential to rat carcinom a cells. Cell, 1991; 65 (1) : Yasuhiro M atsum ura, D avid Tarin. Significance of CD 44 gene p roducts fo r cancer diagno sis and disease e2 valution. L ancet, 1992; 340: Yasuh iro M atsum ura, D am ian H anbury, Jo seph Sm ith, et al. N on- invasive detection of m alignancy by identifi2 cation of unusual CD 44 gene activity in exfo liated can2 cer cells. BM J, 308 (2) : Jan Grondahl- H ansen, Peters HA. P rogno stic signifi2 cance of the recepo r fo r U rokinase P lasm inogen2 activato r in breast cancer. C lin Cancer R es, 1995; 1 (1) : Junji Suzum iya. Comparative study of p lam inogen acti2 vato r antigens in co lonic carcinom as and adenom as. Int J Cancer, 1988; 42 (3) : Kiyashi M o rikaw a. Influence of o rgan environm ent on the grow th selection and m etastasis of hum an co lon carcinom a cell in nude m ice. Cancer R es, 1988; 48 (22) :

5 15. Stetler- stevenson W G, B row n PD, Belin D. T issue in2 hibito r of m etallop ro teinases- 2 (T IM P)mRNA exp res2 sion in tumo r cell lines and hum an tumo r tissues. J B iol Chem, 1990; 265: E lias Campo, T avasso li FA, Charnis A S, et al. Cathep2 sin B exp ression in co lo rectal carcinom as co rrelates w ith tumo r p rogression and sho rtened patients sur2 vival. A m J P athol, 1994; 145 (2) : Christoph Thom ssen. P rogno stic value of the cysteine p ro teinase Cathep sins B and Cathep sins L in hum an breast cancer. C lin Cancer R es, 1995; 1 (7) : Kitadaiy, Bucano CD. M utivariate analysis fo r mrna exp ression of m etastasis- related genes in hum an co lon carcinom a cell. P roceeding of the Am erican association fo r cancer research, 1995; 36: Robert Radinsky, Sem yon R isin. L evel and function of ep iderm al grow th facto r recep to r p redict the m etastatic po tention of hum an co lon carcinom a cells. C lin Cancer R es, 1995; 1 (1) : O ffice of the directo r N C İ N ew direction in mo lecular m edicine Cancer R es, 1994; 54 (2) : N ishizuka Y. Intracellular signo ling by hydro lysis of pho spho lip ids and activation of p ro tein k inase C. S ci2 ence, 1992; 258 (2) : L evy M F. D ecreased levels of PKC enzym e activity and PKCmRNA. D is Colon R ectum, 1993; 36 (6) : M asaru Kuranam l. A nalysis of P ro tien k inase C isofo rm exp ression in a co lo rectal cancer liver m etastasis model. A m er J su rg, 1995; 169 (1) : F lavia M., D i Renzo. O verexp ression and amp lification of the m etgh GF recep to r gene during the p rogression of co lo rectal cancer. C lin Cancer R es, 1995; 1 (2) : N ek re S. Study of c - erbb - 2 p ro tien and ep iderm al grow th facto r recep to r exp ression and DNA p lo idy pat2 tern in co lo rectal carcinom a. J S urg O ncol, 1993; 54 (2) : W u Kastrinakis. Increased incidence of P53 m utations is associted w ith hepatic m etastasis in co lo rectal neop las2 tic p rogression. O ncog ene, 1995; 11 (4) : M itchell H aut, Patricia S. Steeg, Jam es K, et al. Induc2 tion of nm 23 gene exp ression in hum an co lonic neo2 p lasm s and equal exp ression in co lon tumo rs of high and low m etastatic po tential. J N atl Cancer Inst, 1991; 83: Yam aguch ia, U rano T, Fush ida S, et al. Inverse associ2 ation of nm 23- H 1 exp ression by co lo rectal cancer w ith liver m etastasis. B r J Cancer, 1993; 68: Cohn K, Fusheng W ang, F idelina DL, et al. A ssociation of nm 23- H 1 allelic deletions w ith distant m etastases in co lo rectal carcinom a. L ancet, 1991; 338: L im ing W ang. M utation in the nm 23 gene is associated w ith m etastasis in co lo rectal canceṙ Cancer R es, 1993; 53: Carcinogenesis T eratogenesis and M utagenesis V o l 8 N o , , 3 ( 1, 3 - Butadiene,, BD ), BD, (15, 26) (13, 19) BD 20 40, BD, , BD, 5 (13) 1986, 6 5 BD ( IA RC) : (21, 25), BD BD, CT