Abstract #5: Human chorionic gonadotrophin (hCG) prevents the transformation phenotypes induced by 17 \#946;-estradiol in human breast epithelial cells
Authors: Hilal Kocdor, Mehmet Kocdor, Jose Russo, Kara Snider, Johana Vanegas, Irma Russo, Sandra Fernandez
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

The elevated incidence of breast cancer in women has been associated with prolonged exposure to high levels of estrogen and we have demonstrated that 17 \#946;-estradiol (E2) is capable of in vitro transforming the human breast epithelial cell (HBEC) MCF-10F that is ER\#945;-negative (FASEB J 2006;20:1622-34). In the present work we aim to determine whether recombinant human chorionic gonadotrophin (rhCG) prevents the initiation of the neoplastic process induced by E2. The rationale in the use of rhCG is that there is a reduction in breast cancer incidence resulting from early and multiple full-term pregnancies and that rhCG mimics this preventive effect by inducing gland differentiation. For this purpose we studied the effect of the rhCG on the transformation induced by E2. MCF-10F cells were cultured during two weeks in the presence of 70nM E2 alone or in combination with 50IU/ml rhCG. As controls, MCF-10F were treated with DMSO (solvent in which E2 was dissolved) or rhCG alone. At the end of the treatments, the cells were plated in collagen (3-D culture) for detecting two main phenotypes of cell transformation that are the loss of ductulogenic capacity and the concomitant formation of solid masses of cells. In these structures we have determined the length and diameter of the main ducts, the diameter of solid masses, and the number of primary, secondary and tertiary branching arising from main ducts. Analysis of the variance (ANOVA) followed by Tukey\#8217;s test was used for the comparisons of quantitative parameters. We found that E2 significantly increased solid mass formation (both in number and size) (p<0,001) and it also increased the main duct width (p<0,001) although, it did not affect the length and branching of the ducts. E2 also caused a remarkable disruption of the luminal monolayer architecture. The total numbers of ducts were found to be similar between the different groups however, the number of intermediate forms in the E2+rhCG group was significantly higher than the others (p<0,001). In the E2+rhCG group, the number of primary and secondary branching was higher than the control in regular media and DMSO groups (p=0,005; p=0,010). The ducts showed tertiary branching only in the rhCG-treated groups (rhCG and rhCG+E2). In addition, number of tertiary branches in rhCG group was higher than combination (Student\#8217;s t test, p<0,001). Main ductal lengths in rhCG-treated groups (rhCG and rhCG+E2) were significantly longer than the others (p<0,001). In conclusion the rhCG was able to abrogate the transforming abilities of estradiol and it had a differentiating property on the human breast epithelial cells by increasing the branching pattern. These observations indicate that rhCG has significant potential as chemo-preventive agent, protecting the normal cells from becoming malignant. (This study was supported by Grant R21 ES015894-01 from the NIEHS)

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5.