Journal
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Volume 96, Issue 9, Pages E1418-E1426Publisher
OXFORD UNIV PRESS INC
DOI: 10.1210/jc.2011-0473
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Funding
- Centre Hospitalier Universitaire de Nimes [PHRC 2002.162]
- Cancer Science Institute of Singapore
- Chinese Fundamental Research Funds for the Central Universities [WK2070000008]
- Chinese Academy of Sciences [2010T2S03]
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Context: Empirical evidence suggests that autocrine human GH (hGH) may possess a proliferative and oncogenic role in human mammary carcinoma. However, this concept is largely derived from studies using cultured human mammary carcinoma cell (HMCC) lines. Objective: We investigated the expression and functionality of hGH and the hGH receptor in isolated cultures of primary HMCC. Design: Epithelial cell adhesion molecule-positive primary HMCC were isolated from surgical biopsies of patients with mammary carcinoma and cultured in vitro. Expression of hGH and hGH receptor was determined by RT-PCR, immunofluorescence microscopy, and ELISA. The proliferative response of the cultured primary HMCC to hGH stimulation or hGH inhibition with a hGH antagonist was determined. Results: One hundred percent of cultured primary HMCC expressed the hGH receptor, and 52% expressed hGH at the mRNA level. hGH-positive primary HMCC produced hGH protein within the cell and secreted hGH to the media. Both hGH-negative and hGH-positive HMCC responded to hGH stimulation with large increases in cell number. hGH-positive HMCC responded to inhibition of hGH by a hGH antagonist with a decrease in cell number, whereas hGH-negative HMCC did not. Conclusion: Primary HMCC proliferate in response to hGH, and the proliferation of hGH-positive HMCC is inhibited by hGH antagonism. Inhibition of hGH in patients with mammary carcinomamay therefore limit tumor growth. (J Clin Endocrinol Metab 96: E1418-E1426, 2011)
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