Loss of thyrotropin regulation and transforming growth factor beta-induced growth arrest in erbB-2 overexpressing rat thyroid cells.
Amplification of erbB-2 gene and overexpression of gp185erbB-2 gene product is found in approximately one-third of primary human breast and ovarian cancer. Overexpression of gp185erbB-2 was recently found in human papillary thyroid carcinomas, but not in thyroid follicular carcinomas or adenomas. The erbB-2 gene encodes a cell surface growth factor receptor with intrinsic tyrosine kinase activity. Wild type human erbB-2 has been shown to act as a potent oncogene when overexpressed in mouse fibroblasts. To test whether overexpression of normal human erbB-2 gene can transform epithelial differentiated rat thyroid cells, these cells were infected with a recombinant retroviral expression vector containing the erbB-2 protooncogene. Rat thyroid cells expressing high levels of gp185erbB-2 do not display a fully transformed and tumorigenic phenotype. However, the isolated cell clones that overexpress gp185erbB-2, show changes in their growth properties if compared to normal thyroid cells, since they can grow in absence of thyrotropin, the main growth factor controlling thyroid cell proliferation in vitro, and do not respond to the growth inhibitory effect of transforming growth factor beta.
Mincione
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Istituto di Patologia Umana e Medicina Sociale, Facoltà di Medicina e Chirurgia, Chieti, Italy.
Cirafici
A M
AM
Lazzareschi
D
D
Pepe
S
S
Ciardiello
F
F
Colletta
G
G
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002934:Cinnamates; D004351:Drug Resistance; D006921:Hygromycin B / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009856:Oncogene Proteins, Viral / Q000032:analysis* / Q000235:genetics; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D018719:Erb-b2 Receptor Tyrosine Kinases; D011989:Receptors, Thyrotropin / Q000032:analysis; D013961:Thyroid Gland / Q000737:chemistry / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D002934:Cinnamates; D006921:Hygromycin B; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011989:Receptors, Thyrotropin; D016212:Transforming Growth Factor beta; C026273:hygromycin A