Please use this identifier to cite or link to this item: https://doi.org/10.1074/jbc.M109931200
Title: Autocrine human growth hormone inhibits placental transforming growth factor-β gene transcription to prevent apoptosis and allow cell cycle progression of human mammary carcinoma cells
Authors: Graichen, R. 
Liu, D.
Sun, Y.
Lee, K.-O.
Lobie, P.E.
Issue Date: 19-Jul-2002
Citation: Graichen, R., Liu, D., Sun, Y., Lee, K.-O., Lobie, P.E. (2002-07-19). Autocrine human growth hormone inhibits placental transforming growth factor-β gene transcription to prevent apoptosis and allow cell cycle progression of human mammary carcinoma cells. Journal of Biological Chemistry 277 (29) : 26662-26672. ScholarBank@NUS Repository. https://doi.org/10.1074/jbc.M109931200
Abstract: Multiple cellular effects of human growth hormone (hGH) are mediated by an indirect mechanism requiring transcriptional activation of genes encoding protein effector molecules such as insulin-like growth factor-1. Such protein effector molecules then act directly to mediate the cellular functions of hGH. We report here that autocrine hGH production by mammary carcinoma cells specifically results in the transcriptional repression of the p53-regulated placental transforming growth factor-β (PTGF-β) gene. Transcriptional repression of the PTGF-β gene does not require the p53-binding sites in the PTGF-β promoter, and autocrine hGH also desensitized the response of the PTGF-β promoter to p53 overexpression. Transcriptional repression of the PTGF-β gene is accompanied by consequent decreases in its protein product, Smad-mediated transcription, and its cellular effects that include cell cycle arrest and apoptosis. PTGF-β specifically inhibited the autocrine hGH-stimulated expression of cyclin D1 required for autocrine hGH-stimulated mammary carcinoma cell cycle progression. Thus, one mechanism by which autocrine hGH promotes an increase in mammary carcinoma cell number is by transcriptional repression of protein effector molecules that promote cell cycle arrest and apoptosis. Such transcriptional repression of negative regulatory factors, such as PTGF-β, may also be requisite for direct stimulation of mammary carcinoma cell mitogenesis by hGH.
Source Title: Journal of Biological Chemistry
URI: http://scholarbank.nus.edu.sg/handle/10635/111794
ISSN: 00219258
DOI: 10.1074/jbc.M109931200
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

53
checked on Dec 12, 2018

WEB OF SCIENCETM
Citations

54
checked on Dec 12, 2018

Page view(s)

28
checked on Dec 7, 2018

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.