Thyroid hormone decreases the expression of epidermal growth factor receptor.
The receptors for epidermal growth factor (EGF) and thyroid hormone (T3) are prototypes, respectively, of transmembrane signaling proteins and nuclear transcription regulatory proteins. Oncogenic homologs of these two receptor genes, v-erbB and v-erbA, cooperate with each other in cellular transformation and blockage of erythrocytic differentiation. As a first step toward investigating this cooperation, we have studied the relationship between the normal homologs of these two receptors in A431 cells. Treatment of these cells with T3 has no significant effect on EGF receptor gene transcription but leads to a drastic decrease in the steady-state level of receptor mRNA. The down-regulatory effect is visible by 2 h and persists up to 8 h, but EGF receptor mRNA returns to normal (sometimes higher than normal) level by 48-72 h. The T3-induced decrease in EGF receptor mRNA (found during 2-8 h of T3 treatment) is due to a specific destabilization of EGF receptor mRNA. The 5.6-kb mRNA that encodes the full-length transmembrane EGF receptor is preferentially degraded. The half-life of the 2.6-kb mRNA that encodes the aberrant C-terminally truncated receptor is unaffected by T3. In other studies we found that T3 decreases the rate of synthesis of the full-length EGF receptor protein and reduces its steady-state amount. Overall the results demonstrate a negative regulatory effect of T3 in post-transcriptional control of EGF receptor expression, and raise interesting questions regarding the mechanism of this down-regulation, and the possible roles of T3 receptors in the control of EGF receptor function.
Kesavan
P
P
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia 19104.
Mukhopadhayay
S
S
Murphy
S
S
Rengaraju
M
M
Lazar
M A
MA
Das
M
M
D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D015342:DNA Probes; D015536:Down-Regulation; D066246:ErbB Receptors / Q000378:metabolism*; D005809:Genes, Regulator; D006801:Humans; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000032:analysis; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D013963:Thyroid Hormones / Q000378:metabolism*; D014158:Transcription, Genetic
D015342:DNA Probes; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; D066246:ErbB Receptors