RT Book, Section
A1 Park, Morag
A2 Valle, David L.
A2 Antonarakis, Stylianos
A2 Ballabio, Andrea
A2 Beaudet, Arthur L.
A2 Mitchell, Grant A.
SR Print(0)
ID 1181413669
T1 Oncogenes
T2 The Online Metabolic and Molecular Bases of Inherited Disease
YR 2019
FD 2019
PB McGraw-Hill Education
PP New York, NY
SN 9780071459969
LK ommbid.mhmedical.com/content.aspx?aid=1181413669
RD 2024/04/18
AB Oncogenes  are  altered  forms  of  normal  cellular  genes  called  proto-oncogenes.  In  human  cancers,  proto-oncogenes  are  frequently  located  adjacent  to  chromosomal  breakpoints  and  are  targets  for  mutation.  The  products  of  proto-oncogenes  are  highly  conserved  in  evolution  and  serve  to  regulate  the  cascade  of  events  that  maintains  the  ordered  progression  through  the  cell  cycle,  cell  division,  and  differentiation.  In  the  cancer  cell,  this  ordered  progression  is  partially  lost  when  one  or  more  of  the  components  of  this  pathway  are  altered.The  control  of  normal  cell  growth  and  differentiation  is  mediated  by  the  interaction  of  growth  factors  and  cytokines  with  their  membrane-bound  receptors.  This  event  triggers  a  cascade  of  intracellular  biochemical  signals  that  eventually  results  in  the  activation  and  repression  of  various  genes.  Proto-oncogene  products  have  been  shown  to  function  at  critical  steps  in  these  pathways  and  include  proteins  such  as  extracellular  cytokines  and  growth  factors,  transmembrane  growth  factor  receptors,  cytoplasmic  proteins  that  act  to  transmit  the  signal  to  the  nucleus,  and  nuclear  proteins  that  include  transcription  factors  and  proteins  involved  in  the  control  of  DNA  replication.Accumulating  evidence  suggests  that  the  activation  of  several  oncogenes  and  the  inactivation  of  several  growth-suppressor  genes  are  necessary  for  acquisition  of  a  complete  neoplastic  phenotype.  It  has  been  possible  from  experimental  studies  to  subdivide  oncogenes  into  several  groups.  One  class  of  genes  rescues  cells  from  senescence  and  programmed  cell  death;  they  act  as  immortalizing  genes  that  block  cell  differentiation.  A  second  class  of  genes  reduces  growth  factor  requirements  and  induces  changes  in  cell  shape  that  result  in  a  continuous  proliferative  response  that  is  no  longer  regulated.The  use  of  transgenic  mice  is  providing  a  powerful  experimental  approach  to  investigate  the  role  of  oncogenes  in  cancer.  Oncogene  expression  can  be  directed  to  specific  tissues,  where  a  role  for  the  oncogene  in  tumor  formation  in  those  tissues  can  be  evaluated.  Although  transgenic  mouse  strains  carrying  a  single  oncogene  generally  show  an  increased  incidence  of  neoplasia,  oncogene  expression  usually  precedes  tumor  formation  by  many  months,  and  the  tumors  that  result  are  frequently  clonal,  implying  that  other  events  are  necessary.  Examination  of  the  secondary  events  in  tumors  from  oncogene-bearing  transgenic  mice  has  confirmed  the  conclusions  derived  from  in  vitro  studies  and  has  identified  new  oncogenes.  By  crossing  two  strains  of  oncogene-bearing  mice,  the  consequence  of  multiple  oncogenes  on  tumor  incidence  can  be  studied  in  a  host  capable  of  mounting  a  physiological  response.