Leptin - A growth factor in normal and malignant breast cells and for normal mammary gland development

Xin Hu, Subhash C. Juneja, Nita J. Maihle, Margot P. Cleary

Research output: Contribution to journalArticle

355 Citations (Scopus)

Abstract

Background: Obesity is a risk factor for breast cancer in postmenopausal women. As body weight and fat mass increase, circulating leptin increases. Leptin is an adipocyte-derived cytokine that acts through the long form of its receptor, termed OB-Rb. To investigate whether leptin is associated with breast cancer, we determined the expression of OB-Rb in human breast epithelial HBL100 cells and human breast carcinoma-derived T-47D cells, determined whether leptin influenced the proliferation of these cells, and evaluated the structure of mammary tissue in genetically obese leptin-deficient Lepob Lepob and leptin receptor-deficient Leprdb Leprdb mice. Methods: Cell numbers and cell colony formation by HBL100 and T-47D cells were determined by anchorage-dependent and anchorage-independent growth assays. OB-Rb expression was examined by reverse transcription-polymerase chain reaction and immunoblot analyses. Expression of leptin signaling pathway components was evaluated with immunoblot and electrophoretic mobility shift assays. Mammary gland development in lean and obese mice was investigated in whole-mount studies. All statistical tests were two-sided. Results: Leptin enhanced anchorage-dependent proliferation by 138% (95% confidence Interval [CI] = 108% to 169%) in T-47D cells and 50% (95% CI = 38% to 60%) in HBL100 cells. In both cell lines, OB-Rb was expressed, and leptin increased the expression of phosphorylated signal transducers and activators of transcription 3 (STAT3), phosphorylated extracellular signal-regulated kinase (ERK), and transcript activator protein 1 (AP-1). However, leptin increased anchorage-independent cell growth only in the breast cancer cell line (by 81% [95% CI = 62% to 101 %] compared with untreated cells). Obese Lepob Lepob and Leprdb Leprdb mice had minimal epithelial development in the mature mammary gland compared with their lean counterparts. Conclusions: Leptin appears to be able to control the proliferation of both normal and malignant breast epithelial cells. Consequently, the leptin pathway should be further studied as a target for interventions to treat or prevent breast cancer.

Original languageEnglish (US)
Pages (from-to)1704-1711
Number of pages8
JournalJournal of the National Cancer Institute
Volume94
Issue number22
StatePublished - Nov 20 2002

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Human Mammary Glands
Leptin
Intercellular Signaling Peptides and Proteins
Breast
Breast Neoplasms
Leptin Receptors
Confidence Intervals
Epithelial Cells
Cell Line
STAT3 Transcription Factor
Obese Mice
Extracellular Signal-Regulated MAP Kinases
Transcription Factor AP-1
Electrophoretic Mobility Shift Assay
Growth
Adipocytes
Reverse Transcription
Adipose Tissue
Obesity
Cell Count

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Leptin - A growth factor in normal and malignant breast cells and for normal mammary gland development. / Hu, Xin; Juneja, Subhash C.; Maihle, Nita J.; Cleary, Margot P.

In: Journal of the National Cancer Institute, Vol. 94, No. 22, 20.11.2002, p. 1704-1711.

Research output: Contribution to journalArticle

Hu, Xin ; Juneja, Subhash C. ; Maihle, Nita J. ; Cleary, Margot P. / Leptin - A growth factor in normal and malignant breast cells and for normal mammary gland development. In: Journal of the National Cancer Institute. 2002 ; Vol. 94, No. 22. pp. 1704-1711.
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abstract = "Background: Obesity is a risk factor for breast cancer in postmenopausal women. As body weight and fat mass increase, circulating leptin increases. Leptin is an adipocyte-derived cytokine that acts through the long form of its receptor, termed OB-Rb. To investigate whether leptin is associated with breast cancer, we determined the expression of OB-Rb in human breast epithelial HBL100 cells and human breast carcinoma-derived T-47D cells, determined whether leptin influenced the proliferation of these cells, and evaluated the structure of mammary tissue in genetically obese leptin-deficient Lepob Lepob and leptin receptor-deficient Leprdb Leprdb mice. Methods: Cell numbers and cell colony formation by HBL100 and T-47D cells were determined by anchorage-dependent and anchorage-independent growth assays. OB-Rb expression was examined by reverse transcription-polymerase chain reaction and immunoblot analyses. Expression of leptin signaling pathway components was evaluated with immunoblot and electrophoretic mobility shift assays. Mammary gland development in lean and obese mice was investigated in whole-mount studies. All statistical tests were two-sided. Results: Leptin enhanced anchorage-dependent proliferation by 138{\%} (95{\%} confidence Interval [CI] = 108{\%} to 169{\%}) in T-47D cells and 50{\%} (95{\%} CI = 38{\%} to 60{\%}) in HBL100 cells. In both cell lines, OB-Rb was expressed, and leptin increased the expression of phosphorylated signal transducers and activators of transcription 3 (STAT3), phosphorylated extracellular signal-regulated kinase (ERK), and transcript activator protein 1 (AP-1). However, leptin increased anchorage-independent cell growth only in the breast cancer cell line (by 81{\%} [95{\%} CI = 62{\%} to 101 {\%}] compared with untreated cells). Obese Lepob Lepob and Leprdb Leprdb mice had minimal epithelial development in the mature mammary gland compared with their lean counterparts. Conclusions: Leptin appears to be able to control the proliferation of both normal and malignant breast epithelial cells. Consequently, the leptin pathway should be further studied as a target for interventions to treat or prevent breast cancer.",
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N2 - Background: Obesity is a risk factor for breast cancer in postmenopausal women. As body weight and fat mass increase, circulating leptin increases. Leptin is an adipocyte-derived cytokine that acts through the long form of its receptor, termed OB-Rb. To investigate whether leptin is associated with breast cancer, we determined the expression of OB-Rb in human breast epithelial HBL100 cells and human breast carcinoma-derived T-47D cells, determined whether leptin influenced the proliferation of these cells, and evaluated the structure of mammary tissue in genetically obese leptin-deficient Lepob Lepob and leptin receptor-deficient Leprdb Leprdb mice. Methods: Cell numbers and cell colony formation by HBL100 and T-47D cells were determined by anchorage-dependent and anchorage-independent growth assays. OB-Rb expression was examined by reverse transcription-polymerase chain reaction and immunoblot analyses. Expression of leptin signaling pathway components was evaluated with immunoblot and electrophoretic mobility shift assays. Mammary gland development in lean and obese mice was investigated in whole-mount studies. All statistical tests were two-sided. Results: Leptin enhanced anchorage-dependent proliferation by 138% (95% confidence Interval [CI] = 108% to 169%) in T-47D cells and 50% (95% CI = 38% to 60%) in HBL100 cells. In both cell lines, OB-Rb was expressed, and leptin increased the expression of phosphorylated signal transducers and activators of transcription 3 (STAT3), phosphorylated extracellular signal-regulated kinase (ERK), and transcript activator protein 1 (AP-1). However, leptin increased anchorage-independent cell growth only in the breast cancer cell line (by 81% [95% CI = 62% to 101 %] compared with untreated cells). Obese Lepob Lepob and Leprdb Leprdb mice had minimal epithelial development in the mature mammary gland compared with their lean counterparts. Conclusions: Leptin appears to be able to control the proliferation of both normal and malignant breast epithelial cells. Consequently, the leptin pathway should be further studied as a target for interventions to treat or prevent breast cancer.

AB - Background: Obesity is a risk factor for breast cancer in postmenopausal women. As body weight and fat mass increase, circulating leptin increases. Leptin is an adipocyte-derived cytokine that acts through the long form of its receptor, termed OB-Rb. To investigate whether leptin is associated with breast cancer, we determined the expression of OB-Rb in human breast epithelial HBL100 cells and human breast carcinoma-derived T-47D cells, determined whether leptin influenced the proliferation of these cells, and evaluated the structure of mammary tissue in genetically obese leptin-deficient Lepob Lepob and leptin receptor-deficient Leprdb Leprdb mice. Methods: Cell numbers and cell colony formation by HBL100 and T-47D cells were determined by anchorage-dependent and anchorage-independent growth assays. OB-Rb expression was examined by reverse transcription-polymerase chain reaction and immunoblot analyses. Expression of leptin signaling pathway components was evaluated with immunoblot and electrophoretic mobility shift assays. Mammary gland development in lean and obese mice was investigated in whole-mount studies. All statistical tests were two-sided. Results: Leptin enhanced anchorage-dependent proliferation by 138% (95% confidence Interval [CI] = 108% to 169%) in T-47D cells and 50% (95% CI = 38% to 60%) in HBL100 cells. In both cell lines, OB-Rb was expressed, and leptin increased the expression of phosphorylated signal transducers and activators of transcription 3 (STAT3), phosphorylated extracellular signal-regulated kinase (ERK), and transcript activator protein 1 (AP-1). However, leptin increased anchorage-independent cell growth only in the breast cancer cell line (by 81% [95% CI = 62% to 101 %] compared with untreated cells). Obese Lepob Lepob and Leprdb Leprdb mice had minimal epithelial development in the mature mammary gland compared with their lean counterparts. Conclusions: Leptin appears to be able to control the proliferation of both normal and malignant breast epithelial cells. Consequently, the leptin pathway should be further studied as a target for interventions to treat or prevent breast cancer.

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