Involvement of adiponectin and leptin in breast cancer: clinical and in vitro studies

Abstract

Obesity is a risk factor for breast cancer development. A recent hypothesis suggests that the adipokines, adiponectin and leptin, are involved in breast cancer development. This prompted us to investigate the role of adiponectin and leptin in mammary carcinogenesis. Adiponectin receptors (AdipoR1 and AdipoR2) and leptin receptor (Ob-Rt, representing all the isoforms of Ob-R) proteins were detected by immunohistochemistry in in situ ductal carcinoma, invasive ductal malignancy, and healthy adjacent tissue. In addition, mRNA expression of adiponectin, AdipoR1, AdipoR2, leptin, Ob-Rt, and Ob-Rl (the long isoform of Ob-R) was observed in MCF-7 breast cancer cells. Interestingly, leptin mRNA expression was 34.7-fold higher than adiponectin mRNA expression in the MCF-7 cell line. Moreover, adiponectin (10 mg/ml) tended to decrease the mRNA expression of leptin (K36%) and Ob-Rl (K28%) and significantly decreased Ob-Rt mRNA level (K26%). In contrast, leptin treatment (1 mg/ml) significantly decreased AdipoR1 mRNA (K23%). Adiponectin treatment (10 mg/ml) inhibited the proliferation of MCF-7 cells, whereas leptin (1 mg/ml) stimulated the growth of cancer cells. In addition, adiponectin inhibited leptin-induced cell proliferation (both 1 mg/ml). Using microarray analysis, we found that adiponectin reduced the mRNA levels of genes involved in cell cycle regulation (mitogen-activated protein kinase 3 and ATM), apoptosis (BAG1, BAG3, and TP53), and potential diagnosis/prognosis markers (ACADS, CYP19A1, DEGS1, and EVL), whereas leptin induced progesterone receptor mRNA expression.In conclusion, the current study indicates an interaction of leptin-and adiponectin-signaling pathways in MCF-7 cancer cells whose proliferation is stimulated by leptin and suppressed by adiponectin.

Acrp30 inhibits leptin-induced metastasis by downregulating the JAK/STAT3 pathway via AMPK activation in aggressive SPEC-2 endometrial cancer cells

“…T�� ������� �� ��p��� ��� A��p30 ��v��� �� ����v��u���, ������ ���� ��� ��p��� �� A��p30 ��v��� �����, ��� �������� �u�� p�������g���� ����g�� �� ��� ��v���p���� �� ������ (20). L�p��� ��� A��p30 �pp��� �� �x��� ����g������� ����v����� �� downregulating expression of each other's receptor and corre�p�����g ��g�����g p������� (8,39 …”

“…A��p30 �� � 30-�D� p������ ���� ��v���� ��������� ����v�����, including anti-diabetic, anti-inflammatory and anti-atherogenic �u�������, ��� ��� ����� �������� �� ��v� ����-�u��� ������� �� ��v���� ��p�� �� ������ (8). I� �� ��� ���� ��u����� p������ ��������z�� �� ���p��� ����u�, ���� p����� �������������� ���g��g ���� 2 �� 30 µg/�� (9), �u� �� p�����x������ ���u��� �� ������� ��� ��u� g�������� ��u�� �� �� ��g���v��� ���������� ���� ���� ��� ���� (10).…”

Voluntary physical activity counteracts the proliferative tumor growth microenvironment created by adipose tissue via high-fat diet feeding in female rats

“…2010) and LEP has been shown to down regulate AdipoR1 mRNA in breast cancer cells (Jarde et al. 2009). We found that overexpressing AdipoR1 was able to abolish the effects of the HFD‐CM on all cell‐cycle proteins measured (Figs 3 vs. 4) as well as overall cell‐cycle status (Fig.…”

“…2002, 2006; Jarde et al. 2009). LEP is predominately produced by white adipose tissue and its level in the peripheral circulation is directly proportional to BMI (Wauters et al.…”

“…LEP activates several intracellular pathways implicated in breast carcinogenesis, including the phosphoinositide‐3/Akt kinase signaling pathway (Garofalo and Surmacz 2006; Jarde et al. 2009). LEP activates Akt, which phosphorylates p27 at T157, preventing both its nuclear accumulation and inhibition of cyclin E/cdk2, thereby leading to cell‐cycle entry (Dieudonne et al.…”