The potential role of parathyroid hormone-related peptide (PTHrP) as an autocrine growth factor in the regulation of breast cancer cell proliferation
The potential role of parathyroid hormone-related peptide (PTHrP) as an autocrine growth factor in the regulation of breast cancer cell proliferation
We compare the effects of PTHrP (1-34), PTHrP (1-86) and PTH (1-34) on proliferation of two breast cancer cell lines MCF-7 and T-47D. When PTHrP (1-34) binds to a PTH-receptor in osteoblasts it potentially interacts with 1,25 dihydroxycholecalciferol (1,25 DHCC) in regulating bone resorption. By analogy, since 1,25 DHCC receptors are expressed in breast tumour tissue, and 1,25 DHCC inhibits proliferation in vitro, I investigated whether PTHrP might interact with 1,25 DHCC in the regulation of breast cancer cell proliferation. I also investigated the effect of 1,25 DHCC and its analogues (EB 1089, MC 309, 25 HCC) on cells proliferation and their interactions with Epidermal Growth Factor (EGF). Since Epidermal Growth Factor Receptors (EGFRs) are also expressed in breast tumours, I examined the effect of PTHrP on the response to EGF. I also investigated whether PTHrP influenced the expression of EGFR and its potential interaction with and activation of the erbB-2 receptor. Clinically, I immunolocalised PTHrP (1-34), PTHrP (1-86), EGFR and 1,25 DHCC receptors in primary breast tumour tissues and correlated the existent of these parameters with tumour grade, lymph node involvement and the age of the patient.
I showed that PTHrP (1-34) stimulated MCF-7 and inhibited T-47D cell proliferation. However, PTH (1-34) had little or no effect while PTHrP (1-86) had little or the opposite effect to the PTHrP (1-34) peptide. This suggests that alternative types of receptor for PTHrP (1-34) may exist. 1,25 DHCC reduced the response to PTHrP in both cell lines. PTHrP (1-34) inhibited EGF induced proliferation. In contrast PTHrP increased EGF receptor protein level in MCF-7 and decreased it in T-47D cells as evaluated by western analysis.
University of Southampton
Safadi, Mohammed Fayez
6479c1e7-ad4e-4195-af79-0da2769153da
1996
Safadi, Mohammed Fayez
6479c1e7-ad4e-4195-af79-0da2769153da
Safadi, Mohammed Fayez
(1996)
The potential role of parathyroid hormone-related peptide (PTHrP) as an autocrine growth factor in the regulation of breast cancer cell proliferation.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
We compare the effects of PTHrP (1-34), PTHrP (1-86) and PTH (1-34) on proliferation of two breast cancer cell lines MCF-7 and T-47D. When PTHrP (1-34) binds to a PTH-receptor in osteoblasts it potentially interacts with 1,25 dihydroxycholecalciferol (1,25 DHCC) in regulating bone resorption. By analogy, since 1,25 DHCC receptors are expressed in breast tumour tissue, and 1,25 DHCC inhibits proliferation in vitro, I investigated whether PTHrP might interact with 1,25 DHCC in the regulation of breast cancer cell proliferation. I also investigated the effect of 1,25 DHCC and its analogues (EB 1089, MC 309, 25 HCC) on cells proliferation and their interactions with Epidermal Growth Factor (EGF). Since Epidermal Growth Factor Receptors (EGFRs) are also expressed in breast tumours, I examined the effect of PTHrP on the response to EGF. I also investigated whether PTHrP influenced the expression of EGFR and its potential interaction with and activation of the erbB-2 receptor. Clinically, I immunolocalised PTHrP (1-34), PTHrP (1-86), EGFR and 1,25 DHCC receptors in primary breast tumour tissues and correlated the existent of these parameters with tumour grade, lymph node involvement and the age of the patient.
I showed that PTHrP (1-34) stimulated MCF-7 and inhibited T-47D cell proliferation. However, PTH (1-34) had little or no effect while PTHrP (1-86) had little or the opposite effect to the PTHrP (1-34) peptide. This suggests that alternative types of receptor for PTHrP (1-34) may exist. 1,25 DHCC reduced the response to PTHrP in both cell lines. PTHrP (1-34) inhibited EGF induced proliferation. In contrast PTHrP increased EGF receptor protein level in MCF-7 and decreased it in T-47D cells as evaluated by western analysis.
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Published date: 1996
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Local EPrints ID: 459839
URI: http://eprints.soton.ac.uk/id/eprint/459839
PURE UUID: 8619ce41-26ad-4bb7-b75b-1bf0ddadb202
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Date deposited: 04 Jul 2022 17:19
Last modified: 23 Jul 2022 00:58
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Author:
Mohammed Fayez Safadi
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