Cha ra c te riza tio n o f GAGE a ntig e n e xpre ssio n in thirte - PowerPoint PPT Presentation

Cha ra c te riza tio n o f GAGE a ntig e n e xpre ssio n in thirte e n c o mmo n b re a st c a nc e r c e ll line s Pre se nte d b y: Bre nt Vo e ls Ca nkde ska Cika na Co mmunity Co lle g e F o rt T o tte n, No rth Da ko ta

Why is Bre a st Ca nc e r Re se a rc h I mpo rta nt?  Ove r the c o urse o f a life time 1 in 8 wo me n will b e dia g no se d with b re a st c a nc e r.  E stima te s: 200,000 wo me n a re dia g no se d pe r ye a r, a lo ng with 1,700 me n. Appro xima te ly 40,000 wo me n a nd 450 me n die a nnua lly fro m b re a st c a nc e r.  I n the USA wo me n ha ve a 12% c ha nc e o f de ve lo ping inva sive b re a st c a nc e r a t so me po int in the ir live s.  BRCA1 a nd BRCA2 g e ne s a re linke d to a hig h susc e ptib ility o f b re a st c a nc e r b ut o c c ur in o nly 5% o f b re a st c a nc e r pa tie nts.  I n 2006 the c o st o f b re a st c a nc e r tre a tme nt in the US wa s e stima te d to b e $13.9 b illio n do lla rs.  F urthe r re se a rc h ma y pro vide insig ht ino t b re a st c a nc e r pa thwa ys invo lve d in dise a se pro g re ssio n.

GAGE Antig e ns  Cho se n fo r inve stig a tio n b a se d o n pre vio us mic ro a rra y re sults a nd sub se q ue nt inve stig a tio n c o nduc te d a t the Unive rsity o f No rth Da ko ta .  Mic ro a rra y da ta indic a te d tha t the y we re diffe re ntia lly re g ula te d b a se d o n the pre se nc e o r a b se nc e o f the N- a nd C-te rmina l o f MT - 3.  T he g o a l o f this re se a rc h is to c ha ra c te rize the e xpre ssio n o f GAGE fa mily a ntig e ns a c ro ss se ve ra l E R re c e pto r po sitive a nd ne g a tive b re a st c a nc e r c e ll line s.

Wha t a re GAGE Antig e ns?  Be lo ng to a g ro up o f c a nc e r/ te stis a ntig e ns no rma lly e xpre sse d in huma n g e rmline c e lls.  Also fo und to b e e xpre sse d in se ve ra l tumo r type s.  GAGE a ntig e ns fa ll into thre e g ro ups.  GAGE -1 ha s a uniq ue C-te rmina l se q ue nc e no o the r me mb e r ha s.  GAGE s 2 thro ug h 8 a mino a c id se q ue nc e s a re 98% ide ntic a l.  GAGE a ntig e ns ma y dire c t c e ll pro life ra tio n, diffe re ntia tio n, a nd the surviva l o f g e rmline c e lls.  No rma lly e xpre sse d in a dult ma le g e rm c e lls, a nd a sub se t o f o o c yte s in the a dult o va ry.

GAGE Antig e ns a nd Ca nc e r  Pre se nt in 26% o f b re a st c a nc e rs.  Also e xpre sse d in sto ma c h c a nc e r, ne uro b la sto ma , a nd e so pha g e a l c a nc e r.  E xpre ssio n is c o rre la te d to a po o r pro g no sis a nd a g g re ssive tumo r type .  No rma l e xpre ssio n is limite d to immune privile g e d site s ma king the m use ful ta rg e ts fo r pro g no stic indic a to rs.  Po te ntia l ta rg e ts fo r immuno the ra py.

Bre a st Ca nc e r L ine s Cha ra c te rize d  ZR-75-1: E  MCF R+ 7: No MT -3 e xpre ssio n, E R+  ZR-75-30: E R+  T 47D: E R+  VP267: E R-  MDA-MB-157: T riple ne g a tive (No E R,  VP303: E R+ b ut pro g e ste ro ne re c e pto r PR, o r HE R2 re c e pto rs) ne g a tive  MDA-MB-231: T riple ne g a tive (No E R,  SVCT : SV40 T ra nsfo rme d huma n b re a st PR, o r HE R2 re c e pto rs) e pithe lia l c e lls. No n-tumo rig e nic .  MDA-MB-361:  HS578T : T riple ne g a tive .  1-7HB2 I mmo rta lize d no n-tumo r  MT -M223: Hig h a ndro g e n re c e pto r/ lo w fo rming c e ll line . e stro g e n a nd pro g e ste ro ne re c e pto r e xpre ssio n. Dihydro te sto ste ro ne inhib its pro life ra tio n.

T 47D c e ll line sho ws c o nsiste ntly hig h e xpre ssio n No te : Sta tistic s we re no t pe rfo rme d a t this po int. T he re is no sing le c o ntro l g ro up.

GAGE 12B wa s o nly e xpre sse d in the T 47D c e ll line . T he e xpre ssio n wa s a lso lo we r tha n o the r GAGE a ntig e n e xpre ssio n in T 47D c e ll line s.

GAGE 12J ha s the hig he st e xpre ssio n le ve ls in ZR-75-1 c e lls GAGE 13 ha s the hig he st e xpre ssio n le ve ls in VP303 AND MT -M223 c e lls GAGE 06 is e xpre sse d a t a ve ry lo w c o py numb e r in T 47D, MDA-MD-361 a nd ZR-75-01 c e ll line s.

Co nc lusio ns  E  GAGE xpre ssio n is va ria b le a mo ng st the a ntig e n e xpre ssio n is hig hly GAGE a ntig e ns in the c e ll line s va ria b le a mo ng st the c e ll line s te ste d . te ste d .  T he re is no c le a r c o rre la tio n b e twe e n GAGE a ntig e n e xpre ssio n a nd e stro g e n re c e pto r sta tus.  E xpre ssio n o f GAGE 2B,2C,12C, a nd 12D we re hig hly e xpre sse d in T 47D c e lls.

Re se a rc h a t Ca nkde ska  Sinc e 2014 Ca nkde ska ha s a dde d  Ma de po ssib le b y thre e g ra nts $250,000 wo rth o f re se a rc h (NARCH, I NBRE , I CE -T I ) e q uipme nt.  All g ra nts func tio n to hire ST E M  Ca nkde ska is lo o king to e xpa nd fa c ulty, a nd to c o nduc t stude nt drive n re se a rc h. its re se a rc h fa c ilitie s e ve n furthe r.  L  NARCH a nd I o c a l re se a rc h do ne b y lo c a l NBRE suppo rt a te n stude nts. we e k summe r re se a rc h inte rnship.  I CE -T I suppo rts fa c ulty te a c hing a nd re se a rc h in ST E M.