Signal Transduction Laboratory 

Director
John S. Davis, Ph.D.

Ovarian Cancer Research  

The American Cancer Society statistics for ovarian cancer reported that there will be 26,000 new cases and 16,000 deaths in 2004.  The 5-year survival rate for these women is only 15 to 20 percent. The 5-year survival rate for stage I disease patients approaches 90 percent and for stage II disease patients approaches 70 percent. Therefore more sensitive, reliable, effective and unique diagnostic systems are necessary for the detection of early as well as late stage ovarian tumors. 

Since 90% of ovarian cancers are of epithelial origin, mucins may be attractive candidates for the detection of early stage of ovarian cancer. MUC4 mucin expression bears a profound association with ovarian cancer. The central hypothesis of this research is that mucins, particularly MUC4, are associated with the pathogenesis of ovarian cancer. This hypothesis is based on the following preliminary results: I) overexpression of MUC4 in ovarian tumors compared to low/undetectable to none expression in normal tissue and  II) MUC4 is a multifunctional protein that a) promotes cell proliferation by signaling mediated via three EGF domains in the MUC4b subunit, and b) confers anti-adhesive/adhesive properties by covering surface of the tumor cells by MUC4a subunit that is highly O-linked glycosylated.

Study Objectives:

I). Define the incidence of MUC4 expression compared to other mucins (MUC1 and CA125 also known as MUC16) in a large number of ovarian carcinomas in order to establish the sensitivity and specificity of MUC4 expression.

II). Investigate function(s) of MUC4 in ovarian cancer cells by 'overexpression' and 'knock-out' of the MUC4 gene. MUC4 will stably be transfected in MUC4 negative ovarian cell line with MUC4 gene, while MUC4 will be knocked out by siRNA or antisense technology.

III). Determine the significance of co-expression and crosstalk of MUC4 and HER2 in ovarian tumor cells at molecular level MUC4 can be a potential marker for the diagnosis of ovarian cancer.

Conclusions: Based on our preliminary results, we propose that a combined panel of MUC1, MUC4 and MUC16 can offer more sensitive, reliable, effective and unique immunostaining diagnostic system for the detection of early as well as late stage ovarian tumors. MUC4 may serve as a target for the therapy of patients with ovarian cancer.

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