Deregulated expression of cell-cycle proteins during premalignant progression in SENCAR mouse skin.
It is now evident that several genes encoding regulatory activities that control the mammalian cell cycle, particularly some that control the progression of quiescent cells through G1 and into S phase, are targets for alterations that underlie the development of neoplasms. Here, we made a sequential study of alterations in cell cycle protein expression and complex formation among cyclin, cyclin dependent kinases (CDKs) and CDK inhibitors (CKIs) during premalignant progression in SENCAR mouse skin tumors. Changes in the level of expression were observed in positive (cyclin D1, D2, and E2F family members) and negative regulators (p16Ink4a, p57Kip2) of the cell cycle. Also, we observed the formation of cyclin/CDK/CKI complexes. The amounts of these proteins and complexes increased substantially at specific times during promotion but not during malignant conversion to carcinomas. These data show that deregulation of growth control occurs in benign tumors and that subsequent mutations not involved cell-cycle regulation are probably necessary to induce invasive behavior.
Rodriguez-Puebla
M L
ML
The University of Texas MD Anderson Cancer Center, Science Park-Research Division, Smithville 78957, USA.
LaCava
M
M
Gimenez-Conti
I B
IB
Johnson
D G
DG
Conti
C J
CJ
D000818:Animals; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism*; D004268:DNA-Binding Proteins; D018450:Disease Progression; D050684:E2F Transcription Factors; D005260:Female; D051379:Mice; D018632:Mice, Inbred SENCAR; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D038941:Polypyrimidine Tract-Binding Protein; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D056465:Retinoblastoma-Binding Protein 1; D012261:Ribonucleoproteins / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; C493957:Cdkn1a protein, mouse; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D018809:Proliferating Cell Nuclear Antigen; D016601:RNA-Binding Proteins; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D012261:Ribonucleoproteins; D050680:Transcription Factor DP1; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D038941:Polypyrimidine Tract-Binding Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases