Buenos Aires
Breast Cancer
Symposium

BA-BCS 2024

September 3 – 6, 2024

IFIBYNE Auditorium, FCEN-UBA

Poster No. 22

Triple-Negative Breast Cancer: effects of Tamoxifen in the lysosomal pathway

Laura Pereyra1, Lorena Carvelli1,3, Laura Vargas Roig2,4, Miguel Sosa1,3,4

1.Instituto de Histología y Embriología- CONICET 2.Instituto de Medicina y Biología Experimental- CONICET 3.Facultad de Ciencias Exactas y Naturales- UNCuyo 4. Facultad de Medicina- UNCuyo.

Presenting Autor:
Pereyra, Laura Lucía

Instituto de Histología y Embriología de Mendoza (IHEM)- CONICET

Triple-negative breast cancer (TNBC) is a common cancer in women, accounting for 10–15% of all breast cancers. It’s characterized by a poor prognosis and metastatic patterns and is associated with distant recurrence and a high risk of death. TNBC is an attractive research focus for oncology, because no therapeutic target has been found to date.
Cells of some tumors have increased the lysosomal biogenesis as response to its altered metabolism. These events affect lysosomal integrity and/or functionality, where increased levels of lysosomal proteases are observed. Tamoxifen (TAM) treatment of estrogen receptor (ER)-positive breast cancer reduces mortality by modulating hormone dependance of those tumours. However, TAM exerts effects by mechanisms other than interaction with ERs.
Breast cancer cells lines MDA-MB-231 (ER-negative, RP-negative and HER-2 negative) and MCF-7 (ER-positive, PR-positive and HER-2 negative) were incubated with 2 and 10 μM of TAM for 8 and 24 h, in presence or absence of 17-β-estradiol. After the treatments, we used LysotrackerTM Red DND-99 which provides fluorescence detection for live-cell staining of labeling acidic organelles such as lysosomes. We obtained the images using fluorescense mycroscopy and analize them using the software ImageJ. TAM tended to decrease the acidic compartments (AC) after 8 h in both cell lines, but the number of AC was recovered in the MDA-MB-231 cells at 24 h. This effect is more notorious to higher concentrations of TAM (10 μM) in triple negative cell line. This pronounced effect in the triple-negative cells might be influenced by differences in genomic expression, although further research is needed to confirm that. No differences were found in AC in presence of 17-β-estradiol alone in both cell lines. This indicates that TAM could act as lysosomotropic drug in breast cancer cells, independently of ER pathway.