PMID- 9794240
OWN - NLM
STAT- MEDLINE
DCOM- 19981112
LR  - 20190607
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 17
IP  - 12
DP  - 1998 Sep 24
TI  - RET cooperates with RB/p53 inactivation in a somatic multi-step model for murine 
      thyroid cancer.
PG  - 1625-8
AB  - Mice bred to carry germline Rb and p53 null alleles are associated with a tumor 
      spectrum that overlaps with the inherited multiple endocrine neoplasia-1 (MEN1) 
      and MEN2 syndromes in humans, including medullary thyroid cancer (MTC). To study 
      the genetic basis for these tumors, we microdissected MTC specimens or obtained 
      fresh MTC tissue from nine independent Rb(+/-) p53(+/-) mice, amplified the 
      region of the Ret gene known to be mutated in human MTC, and detected acquired 
      missense Ret mutations in four different mice. These mutations were localized to 
      a group of tandem cysteines which are analogous to activating germline mutations 
      observed in human MEN2A and familial MTC (FMTC). To determine whether the 
      remaining wild type Rb allele was inactivated in these murine MTC samples, we 
      subjected tumor tissue to immunohistochemical staining with an Rb antibody, and 
      demonstrated the absence of RB staining in murine MTC, while normal tissue 
      retained RB nuclear staining. These findings demonstrate the ability of the gene 
      knockout model to recapitulate somatic multi-step tumorigenesis and suggest that 
      the development of a murine neuroendocrine tumor requires mutational 
      dysregulation within both receptor tyrosine kinase and nuclear tumor suppressor 
      gene pathways.
FAU - Coxon, A B
AU  - Coxon AB
AD  - Department of Genetics, National Cancer Institute and National Naval Medical 
      Center, Bethesda, Maryland 20889, USA.
FAU - Ward, J M
AU  - Ward JM
FAU - Geradts, J
AU  - Geradts J
FAU - Otterson, G A
AU  - Otterson GA
FAU - Zajac-Kaye, M
AU  - Zajac-Kaye M
FAU - Kaye, F J
AU  - Kaye FJ
LA  - eng
PT  - Journal Article
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Drosophila Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Retinoblastoma Protein)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-ret)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Ret protein, Drosophila)
RN  - EC 2.7.10.1 (Ret protein, mouse)
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - *Drosophila Proteins
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunohistochemistry
MH  - Mice
MH  - Multiple Endocrine Neoplasia Type 1/genetics
MH  - Mutation
MH  - Proto-Oncogene Proteins/*genetics/physiology
MH  - Proto-Oncogene Proteins c-ret
MH  - Receptor Protein-Tyrosine Kinases/*genetics/physiology
MH  - Retinoblastoma Protein/analysis/*genetics
MH  - Thyroid Neoplasms/*genetics/pathology
MH  - Tumor Suppressor Protein p53/analysis/*genetics
EDAT- 1998/10/30 00:00
MHDA- 1998/10/30 00:01
CRDT- 1998/10/30 00:00
PHST- 1998/10/30 00:00 [pubmed]
PHST- 1998/10/30 00:01 [medline]
PHST- 1998/10/30 00:00 [entrez]
AID - 10.1038/sj.onc.1202381 [doi]
PST - ppublish
SO  - Oncogene. 1998 Sep 24;17(12):1625-8. doi: 10.1038/sj.onc.1202381.