PMID- 7956909
OWN - NLM
STAT- MEDLINE
DCOM- 19941216
LR  - 20071114
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 135
IP  - 5
DP  - 1994 Nov
TI  - Transforming growth factor-beta 1 induces growth inhibition of a human medullary 
      thyroid carcinoma cell line despite an increase in steady state c-myc messenger 
      ribonucleic acid levels.
PG  - 1887-93
AB  - Medullary thyroid cancer (MTC) is an endocrine tumor of the thyroid C-cells which 
      provides an important experimental model for studies of tumor differentiation and 
      progression. We investigated the effects of transforming growth factor-beta 1 
      (TGF beta 1) on the growth and functional characteristics of a human medullary 
      thyroid carcinoma cell line (TT). Because the c-myc protooncogene may play an 
      important role in the growth inhibition induced by TGF beta 1, we also assessed 
      steady state c-myc messenger RNA (mRNA) levels in these cells. A 6-day exposure 
      of TT cells to TGF beta 1 resulted in a dose-dependent inhibition of cell 
      proliferation. In addition, TGF beta 1 exposure led to a 3-fold increase in 
      nonadherent floating TT cells in the culture supernatants. The floating cells 
      exhibited ultrastructural features of dying or apoptotic cells, including 
      chromatin condensation, cytoplasmic and nuclear vesicularization, and DNA 
      degradation with evidence of internucleosomal DNA "laddering." Despite inhibition 
      of cell proliferation, steady state c-myc mRNA levels were 3.6 +/- 0.6-fold 
      higher in cells exposed to TGF beta 1 compared to those in control cells (P < 
      0.001). Exposure of cells to a 15-base antisense c-myc oligonucleotide (10 
      microM) resulted in an attenuation of the TGF beta 1-induced growth inhibition 
      and induction of cell death. TGF beta 1 also resulted in an approximately 3-fold 
      decrease in steady state calcitonin and calcitonin gene-related peptide mRNA 
      levels. Finally, using a sensitive bioassay for TGF beta, TT cells were shown to 
      produce and activate significant amounts of TGF beta, particularly under 
      conditions of serum deprivation. Our data thus indicate that TGF beta 1 has 
      multiple effects on TT cell growth and function. It induces growth inhibition in 
      the presence of an increase in steady state mRNA levels of the c-myc 
      protooncogene, which is usually associated with cell proliferation. In addition, 
      TGF beta 1 accelerates apoptosis in TT cells.
FAU - Khosla, S
AU  - Khosla S
AD  - Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905.
FAU - Oursler, M J
AU  - Oursler MJ
FAU - Schroeder, M J
AU  - Schroeder MJ
FAU - Eberhardt, N L
AU  - Eberhardt NL
LA  - eng
GR  - DK-41206/DK/NIDDK NIH HHS/United States
GR  - KO8NS01562/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transforming Growth Factor beta)
SB  - IM
MH  - Base Sequence
MH  - Blotting, Northern
MH  - Carcinoma, Medullary/*chemistry/*pathology/ultrastructure
MH  - Cell Division/drug effects/physiology
MH  - Cell Transformation, Neoplastic/pathology
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Microscopy, Electron
MH  - Molecular Sequence Data
MH  - Proto-Oncogene Proteins c-myc/analysis/*genetics/physiology
MH  - RNA, Messenger/*analysis/genetics/metabolism
MH  - Thyroid Neoplasms/*chemistry/*pathology/ultrastructure
MH  - Transforming Growth Factor beta/*pharmacology
MH  - Tumor Cells, Cultured
EDAT- 1994/11/01 00:00
MHDA- 1994/11/01 00:01
CRDT- 1994/11/01 00:00
PHST- 1994/11/01 00:00 [pubmed]
PHST- 1994/11/01 00:01 [medline]
PHST- 1994/11/01 00:00 [entrez]
AID - 10.1210/endo.135.5.7956909 [doi]
PST - ppublish
SO  - Endocrinology. 1994 Nov;135(5):1887-93. doi: 10.1210/endo.135.5.7956909.