Gene expression of pinc, stat6, gata3 and tbx3 is modified according to the differential breast milk intake in rats

SANTIANO, F.E.; CAMPO VERDE ARBOCCO, F.; SASSO, C.V.; ZYLA, L.E.; ESTALLES, P.E.; PISTONE-CREYDT, V.; LÓPEZ-FONTANA, C.M.; CARON, R.W

Mendoza

Congreso; XXXIV Reunión Científica anual de la Sociedad de Biología de Cuyo; 2016

Sociedad de Biología de Cuyo

The development of the mammary gland occurs after birth. Breast milk consumption can cause changes in the mammary epithelium of the offspring that result in the expression of molecules involved in the induction of differentiation, reducing the risk of developing breast cancer in later life. STAT6 stimulates alveolar differentiation and proliferation potentially due to the transcriptional induction of GATA3. Together, STAT6 and GATA3, induce proliferation and change of the luminal cell to an alveolar lineage. PINC expression has been associated with inhibition of terminal differentiation of mammary alveolar cells. The proposed objective was to analyze whether adequate breastfeeding generates modifications in the expression of genes involved in mamary differentiation. We use Sprague Dawley female rats divided into litters of 3 (C3), 8 (C8) and 12 (C12) pups per mother. At 55 days of age, half of the animals was sacrificed to study the mammary differentiation by whole mount and real-time PCR. The number and size of terminal end buds were significantly lower in C3 versus C8 and C12 demonstrating its greater differentiation state. Using real time PCR, we analyzed the expression of mammary PINC, Tbx3, STAT6, GATA3 and PTEN genes. mRNA of PINC was increased in C12 with respect to C3 and C8. The expression of Tbx3, a protein necessary for the normal development of murine mammary epithelial, and GATA3 and STAT6, were significantly diminished in C12 compared to C3. On the other hand, the rest of the animals were treated with a single dose of dimethylbenzanthracene (15mg / rat) to study latency, incidence and tumor progression. A lower incidence and greater latency were observed in C3 respect to the other groups. These results demonstrate a direct link between milk consumption and the ability of the mammary gland to activate gene programs associated with cell differentiation, which may decrease mammary carcinogenesis.