Abstract
One of the factors that has increased the incidence and worse prognosis of breast cancer is obesity. In this condition, high amounts of leptin are secreted, which have proliferative, mitogenic, antiapoptotic, and proinflammatory activity that may be antagonistic to treatment with tamoxifen, considered the first choice. The modulation evaluation of leptin receptor expression in the presence of leptin and tamoxifen stimuli was performed in breast cancer cell lines MCF 7, MDA MB 231 and HCC 1937 as a model of initial approach for the study of breast cancer subtypes and their behavior to the action response of adipokines and their possible relationship with the mechanism of resistance to chemotherapeutics such as tamoxifen in ER positive cell lines and triple negative marker. It was determined that leptin increases the proliferation of the three breast cancer cell lines and tamoxifen is able to exert an antiproliferative effect on them, however, it was identified that the ability of tamoxifen to decrease the proliferation of cancer cells is diminished in the presence of leptin, in addition to changes in the modulation of the expression of its receptor. It was determined that tamoxifen induces a greater modulation of the expression of ObRb in cell lines, which may be related to the decrease of its antiproliferative activity, while leptin generates a proliferative effect in the three cell lines and could participate in the tamoxifen treatment resistance mechanism.
Highlights
One of the factors that has increased the incidence and worse prognosis of breast cancer is obesity
In the MCF7 cell line, the presence of mRNA of the four genes of interest was found, in the MDA MB 231 cell line only mRNA of the general homologous form of the leptin receptor was found and in the HCC 1937 cell line the expression of the leptin receptor was detected in its two variants
In the cultures of the three different breast cancer cell lines, a positive proliferative effect was observed by stimulation with leptin, the opposite effect was observed when stimulating with tamoxifen (Fig. 3)
Summary
One of the factors that has increased the incidence and worse prognosis of breast cancer is obesity. Breast cancer can be classified into different subtypes depending on the expression pattern of some receptors, such as estrogen (ER), progesterone (PR) and human epidermal growth factor type 2 (Her-2), giving rise to luminal breast cancer A (ER+, PR+), luminal B (ER+, PR+), Her-2 positive and triple negative marker. This classification is very useful to identify the type of chemotherapeutic treatment that should be administered, as well as the degree of risk and prognosis of the condition[2]. There are different mechanisms by which obesity has been linked to cancer, among which are the promotion of inflammation and angiogenesis through the release of some molecules by adipocytes such as fibroblast growth factor (FGF2), angiopoietin-2, angiostatin, endostatin, thrombospondin (TSP-1), resistin, and elevated levels of adipokines such as leptin, among others[5]
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