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Inhibition of oncogene STAT3 phosphorylation by a prolactin antagonist, hPRL-G129R, in T-47D human breast cancer cells
- Source :
- International journal of oncology. 17(6)
- Publication Year :
- 2000
-
Abstract
- We have previously demonstrated that a hPRL antagonist (hPRL-G129R) was able to inhibit PRL induced breast cancer cell proliferation through induction of apoptosis. In the present study, we test the hypothesis that the inhibitory effect of hPRL-G129R in breast cancer cells occurs, at least in part, through the inhibition of oncogene STAT3 activation. We first demonstrated that STAT5 and STAT3 could be activated by either hGH or hPRL in T-47D breast cancer cells. Although the patterns of STAT5 activation by hGH and hPRL are similar, we observed a nearly 10-fold greater efficacy of hPRL in STAT3 activation as compared to that of hGH. More importantly, we have demonstrated that activation of STAT3 by hPRL could be inhibited by hPRL-G129R. Since T-47D cells coexpress GHR and PRLR, an attempt was made to dissect the molecular events mediated through hGHR or hPRLR using mouse L-cells expressing a single population of receptors (hGHR or hPRLR). To our surprise, only STAT5, not STAT3 phosphorylation was observed in these L-cells. In conclusion, our results suggest that: a) STAT3 is preferably activated through hPRLR in T-47D cells; b) hPRL-G129R is effective in inhibiting STAT3 phosphorylation; and c) the mechanism of STAT3 activation is different from that of STAT5.
- Subjects :
- STAT3 Transcription Factor
Cancer Research
medicine.medical_specialty
Antineoplastic Agents, Hormonal
Receptors, Prolactin
Recombinant Fusion Proteins
Population
Breast Neoplasms
Biology
Mice
Hormone Antagonists
L Cells
Internal medicine
medicine
STAT5 Transcription Factor
Tumor Cells, Cultured
Animals
Humans
Phosphorylation
education
Receptor
STAT5
education.field_of_study
Oncogene
Dose-Response Relationship, Drug
Human Growth Hormone
Cancer
Oncogenes
Receptors, Somatotropin
Cell cycle
medicine.disease
Milk Proteins
Neoplasm Proteins
Prolactin
DNA-Binding Proteins
Endocrinology
Oncology
Amino Acid Substitution
Cancer cell
biology.protein
Cancer research
Trans-Activators
Female
Protein Processing, Post-Translational
Subjects
Details
- ISSN :
- 10196439
- Volume :
- 17
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- International journal of oncology
- Accession number :
- edsair.doi.dedup.....5088e1bdfee1edd576782a17343dce8f