26018

LRIG1

LIG-1|LIG1;leucine-rich repeats and immunoglobulin-like domains 1;LRIG1;leucine-rich repeats and immunoglobulin-like domains 1

leucine-rich repeat protein LRIG1|leucine-rich repeats and immunoglobulin-like domains protein 1|ortholog of mouse integral membrane glycoprotein LIG-1

3p14

protein-coding

The aim is to evaluate LRIG1 as a prognosis predictor and correlations to cofactors in squamous cell cervical cancer. LRIG1 expression was studied in 128 cervical carcinomas and was compared with expression of nine other tumor markers. Smoking history was registered and pretreatment serum estradiol and progesterone levels were evaluated in 79 women. At clinical stage IB, 58% of the tumors showed LRIG1 expression, but there was a decline by increasing stage (33% in stage IV). Ninety percent of women with stage IB cancer and LRIG1 positivity survived, as compared to 64% without expression (P = 0.02). LRIG1 expression did not predict prognosis in advanced stages, but in stage IIA there was a marked relative difference, with 75% survival in tumors expressing LRIG1, as compared to 43% in those without. No correlation was found between LRIG1 and the other nine tumor markers studied. A high serum progesterone and smoking correlated to absent LRIG1 expression. We conclude that LRIG1 appears to be a significant prognosis predictor in early-stage cervical cancer, independent of the other tumor markers that were studied. Diminished expression in advanced stages and the inverse correlation to serum progesterone and smoking indicates that LRIG1 is a tumor suppressor in cervix.

The ErbB2 receptor tyrosine kinase is overexpressed in approximately 25% of breast tumors and contributes to poor patient prognosis and therapeutic resistance. Here, we examine the role of the recently discovered ErbB negative regulator LRIG1 in ErbB2(+) breast cancer. We observe that LRIG1 protein levels are significantly suppressed in ErbB2-induced mammary tumors in transgenic mice as well as in the majority of ErbB2(+) human breast tumors. These observations raise the possibility that LRIG1 loss could contribute to the initiation or growth of ErbB2(+) breast tumors. RNA interference-mediated knockdown of endogenous LRIG1 in the ErbB2-overexpressing breast tumor cell lines MDA-MB-453 and BT474 further elevates ErbB2 in these cells and augments cellular proliferation. In contrast, ectopic expression of LRIG1 reverses these trends. Interestingly, we observe that LRIG1 protein levels are suppressed in response to ErbB receptor activation in breast tumor cells but are unaffected by ErbB activation in immortalized nontransformed breast epithelial cells. Our observations indicate that the suppression of LRIG1 protein levels is a common feature of breast tumors. Moreover, our observations point to the existence of a feed-forward regulatory loop in breast tumor cells where aberrant ErbB2 signaling suppresses LRIG1 protein levels, which in turn contributes to ErbB2 overexpression.