The regulation of LIV‐1 mRNA in MDA‐MB‐231 human breast cancer cells and its association with E‐cadherin

Abstract

LIV‐1 is an estrogen‐regulated gene encoding a member of the ZIP family of zinc transporters (SLC39A6). It is expressed in both estrogen‐receptor positive and negative breast cancer cells. In estrogen‐receptor positive MCF‐7 breast cancer cells, LIV‐1 expression is induced by both estrogen and insulin. LIV‐1 has also been observed to induce the expression of the cell adhesion protein E‐cadherin, thought to play a role in metastasis. In the present study, we investigated the regulation of LIV‐1 and its relationship to E‐cadherin in MDA‐MB‐231estrogen‐receptor negative breast cancer cells. Cells were treated with insulin and EGF for 24 h and the mRNA concentrations of LIV‐1 and E‐cadherin were analyzed by RT‐PCR. EGF treatment induced LIV‐1 mRNA by about 2‐fold whereas insulin increased expression only to a minor extent. The mRNA expression of E‐cadherin paralleled that of LIV‐1 with these treatments. MDA‐MB‐231 cells were also transfected with an shRNA construct designed to knock down LIV‐1 expression. This procedure reduced LIV‐1 mRNA concentrations by 30% and expression of E‐cadherin was reduced to a similar extent. This association between LIV‐1 and E‐cadherin expression in MDA‐MB‐231 cells suggests that LIV‐1 may be a regulator of E‐cadherin in both estrogen‐receptor positive and negative cells. The presence of LIV‐1 could serve as a prognostic marker for breast cancer patients with invasive tumors.

Zinc transporter LIV1: A promising cell surface target for triple negative breast cancer

“…T47D (Luminal A molecular subtype) breast cancer cells showed over‐expression of LIV1, confirming that this cell line model is suitable for studying the operative implications of abnormally regulated LIV1 in breast carcinoma (Chong, 2011; Lopez & Kelleher, 2010). Higher levels of LIV1 expression (about 4−8‐fold) was stimulated upon estrogen (trans‐hydroxytamoxifen) treatment in MCF7 and ZR75 breast cancer cell lines positive for estrogen receptor (luminal cell lines) (Guerinot, 2021).…”

“…Cancer cells are wired with the ability to invade and metastasize to other parts. These powerful features drive cell detachment and T A B L E 4 Virtual data analysis using cBioPortal showing percentages of specific alterations in different breast cancer studies requires to be clarified (Chong, 2011).…”

“…LIV1 suppression with short hairpin RNA resulted in lower E‐cadherin expression, indicating a positive relationship between LIV1 and E‐cadherin. However, the significance of SNAI2 in signal transmission between LIV1 and E‐cadherin still requires to be clarified (Chong, 2011).…”

“…A negative link between LIV1 protein expression and tumor grade, stage, and size indicates that LIV1 protein levels are associated with lower aggressive cancers. Elevated expression of LIV1 in less aggressive tumors was attributed due to the elevated expression of E‐Cadherin (Chong, 2011). In another study, LIV1 mRNA levels and protein expression intensity were assessed in large ER+ breast cancer cohorts ( n = 1980 and n = 670 respectively).…”