PMID- 12702553
OWN - NLM
STAT- MEDLINE
DCOM- 20030516
LR  - 20220409
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 63
IP  - 8
DP  - 2003 Apr 15
TI  - Invade or proliferate? Two contrasting events in malignant behavior governed by 
      p16(INK4a) and an intact Rb pathway illustrated by a model system of basal cell 
      carcinoma.
PG  - 1737-42
AB  - Using a highly infiltrative tumor type as basal cell carcinoma as the model 
      system, we have examined the relation between invasive behavior and 
      proliferation. Our results studying alterations in G(1)-S cell cycle regulatory 
      proteins and proliferation in infiltrative cells were surprising and clearly 
      indicated that invasion in tumors with an intact p16(INK4a)-cyclin 
      D-retinoblastoma protein (Rb) pathway was equivalent to ceased proliferation. 
      Using immunohistochemistry and Western blotting of microdissected parts of basal 
      cell carcinomas, we showed that p16(INK4a) was up-regulated at the invasive front 
      of the majority of basal cell carcinomas with infiltrative growth patterns, 
      followed by ceased proliferation, as well as decreased phosphorylation of Rb. 
      Besides supporting the fact that basal cell carcinomas have an intact Rb pathway, 
      our results clearly indicate that invasive tumor cells change phenotype from a 
      proliferative state to an invasive phenotype. Thus, invasion is not necessarily 
      analogous with proliferation, implicating a paradigm shift in the understanding 
      of two central processes in malignant behavior.
FAU - Svensson, Sofie
AU  - Svensson S
AD  - Department of Laboratory Medicine, Division of Pathology, Lund University, Malmo 
      University Hospital, Sweden.
FAU - Nilsson, Kristina
AU  - Nilsson K
FAU - Ringberg, Anita
AU  - Ringberg A
FAU - Landberg, Goran
AU  - Landberg G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Cyclin D)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (Cyclins)
RN  - 0 (Retinoblastoma Protein)
SB  - IM
MH  - Blotting, Western
MH  - Carcinoma, Basal Cell/metabolism/*pathology
MH  - Cell Division/physiology
MH  - Cyclin D
MH  - Cyclin-Dependent Kinase Inhibitor p16/biosynthesis/metabolism/*physiology
MH  - Cyclins/metabolism/physiology
MH  - Humans
MH  - Immunohistochemistry
MH  - Neoplasm Invasiveness
MH  - Retinoblastoma Protein/metabolism/*physiology
MH  - Skin Neoplasms/metabolism/*pathology
MH  - Up-Regulation
EDAT- 2003/04/19 05:00
MHDA- 2003/05/17 05:00
CRDT- 2003/04/19 05:00
PHST- 2003/04/19 05:00 [pubmed]
PHST- 2003/05/17 05:00 [medline]
PHST- 2003/04/19 05:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2003 Apr 15;63(8):1737-42.