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International Journal of Cancer Research
  Year: 2007 | Volume: 3 | Issue: 2 | Page No.: 92-102
DOI: 10.3923/ijcr.2007.92.102
 
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Level of Expression of Parathyroid Hormone Related Protein and its Receptor in Human Breast Cancer and its Correlation with the Clinical Outcome
Mohammad K. Zia, Khaled A. Rmali, Robert E. Mansel and Wen G. Jiang

Abstract:
In this study we examined the level of the expression of PTHrP and its receptor (PTHrP-R) in human breast cancer and correlated their level of expression with the clinical outcome. Primary Breast cancer samples (n = 124) and adjacent non-cancerous breast tissues obtained from patients in cohort (n = 30) were processed for RNA extraction and cDNA synthesis. Levels of expression were assessed quantitatively by Q-PCR and were analyzed against tumour’s stage, grade, nodal status, local relapse, distant metastasis and survival after a median follow-up of 120 months period. Tissue distribution of PTHrP and its receptor (PTHrP-R) protein in human breast cancer tissues were assessed using immunohistochemical analysis. Breast tumour tissues had significantly higher levels of PTHrP transcript compared with normal tissues (breast cancer 64.2±32 copies vs normal tissue 19.4±8.5 copies; p = 0.05). The levels of PTHrP transcript were high in node positive tumours (117±74 copies) compared to node negative tumours (24.8±8.7), although the difference was not statistically significant (p = 0.23). Increased levels of PTHrP mRNA expression appears to be positively correlated with disease progression as levels were high in samples of patients who had distant metastasis (66.5± 64; p = 0.56) and/or die of breast related causes (306±23.5; p = 0.26) when compared to those who were disease free (25.9±8). PTHrP expression was also increased with increasing grade and TNM status. No difference of PTHrP-R levels was found between normal and tumour tissues (p = 0.73), node negative and positive tumours (p = 0.15). Ductal carcinomas had a higher level of PTHrP transcripts (75±39 copies), compared with less malignant lobular (17±12). However, ductal carcinomas had a lower level PTHrP-R (1.7+0.4) than lobular carcinomas (7.6±7.0). PTHrP and PTHrP-R staining was cytoplasmic as well as showed some degree of staining in the nuclei. Tumour cells displayed stronger staining compared with normal mammary epithelial cells. We conclude that here, PTHrP expression is increased in human breast cancer, particularly in patients with aggressive tumours and with mortality. Over-expression of PTHrP in breast cancer cells result in more aggressive phenotype. Together, it suggests that PTHrP plays a role beyond the initial metastasis repressor and is involved in disease progression in this cancer type.
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How to cite this article:

Mohammad K. Zia, Khaled A. Rmali, Robert E. Mansel and Wen G. Jiang, 2007. Level of Expression of Parathyroid Hormone Related Protein and its Receptor in Human Breast Cancer and its Correlation with the Clinical Outcome. International Journal of Cancer Research, 3: 92-102.

DOI: 10.3923/ijcr.2007.92.102

URL: https://scialert.net/abstract/?doi=ijcr.2007.92.102

 
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