Neoplastic transformation of rat thyroid cells requires the junB and fra-1 gene induction which is dependent on the HMGI-C gene product.
The expression of the high mobility group I (HMGI)-C chromatin component was shown previously to be essential for the establishment of the neoplastic phenotype in retrovirally transformed thyroid cell lines. To identify possible targets of the HMGI-C gene product, we have analyzed the AP-1 complex in normal, fully transformed and antisense HMGI-C-expressing rat thyroid cells. We show that neoplastic transformation is associated with a drastic increase in AP-1 activity, which reflects multiple compositional changes. The strongest effect is represented by the dramatic junB and fra-1 gene induction, which is prevented in cell lines expressing the antisense HMGI-C. These results indicate that the HMGI-C gene product is essential for the junB and fra-1 transcriptional induction associated with neoplastic transformation. The inhibition of Fra-1 protein synthesis by stable transfection with a fra-1 antisense RNA vector significantly reduces the malignant phenotype of the transformed thyroid cells, indicating a pivotal role for the fra-1 gene product in the process of cellular transformation.
Vallone
D
D
Istituto Internazionale di Genetica e Biofisica, CNR, via Guglielmo Marconi 12, I-80125 Naples, Italy.
Battista
S
S
Pierantoni
G M
GM
Fedele
M
M
Casalino
L
L
Santoro
M
M
Viglietto
G
G
Fusco
A
A
Verde
P
P
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D025743:HMGA2 Protein; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D016372:RNA, Antisense; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D051381:Rats; D013961:Thyroid Gland / Q000166:cytology; D013964:Thyroid Neoplasms / Q000235:genetics*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015533:Transcriptional Activation; D000099169:Fos-Related Antigen 1
D025743:HMGA2 Protein; D006609:High Mobility Group Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016372:RNA, Antisense; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018808:Transcription Factor AP-1; D000099169:Fos-Related Antigen 1