Immune-surveillance and programmed cell death-related genes are significantly overexpressed in the normal breast epithelium of postmenopausal parous women

  • Authors:
    • G. A. Balogh
    • I. H. Russo
    • C. Spittle
    • R. Heulings
    • J. Russo
  • View Affiliations

  • Published online on: August 1, 2007     https://doi.org/10.3892/ijo.31.2.303
  • Pages: 303-312
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Endocrine and reproductive influences significantly affect the lifetime risk of breast cancer. Nulliparity is one of the most firmly established risk factors for breast cancer, whereas early full-term pregnancy and parity confer a significant protection. The breast attains its maximum development during pregnancy and lactation. After menopause the breast regresses in both nulliparous and parous women containing lobular structures designated lobules type 1 (Lob 1). We have postulated that the degree of differentiation acquired through early pregnancy changes the ‘genomic signature’ that differentiates the Lob 1 from the early parous women from that of the nulliparous women by shifting the Stem cell 1 to a Stem cell 2, making this the mechanism of protection conferred by early full-term pregnancy. In order to elucidate the molecular pathways through which pregnancy exerts a protective effect, we have analyzed the genomic profile of Lob 1 present in reduction mammoplasty specimens obtained from parous and nulliparous postmenopausal women. The genes differentially expressed are related to immune-surveillance, DNA repair, programmed cell death, transcription, and chromatin structure/activators/co-activator. In the present study we performed real-time RT-PCR using a low-density array or a microfluid card for genes related to the immune system and programmed cell death, using 18S as an internal control [TaqMan® Low Density Array Human Immune Panel (Applied Biosystems)]. Breast epithelial cells from parous women significantly overexpressed 17 out of 20 genes (p<0.001) with respect to the nulliparous breast. BCL2-associated X protein, Complement component 3, CD45 antigen, glyceraldehyde-3-phosphate dehydrogenase, granulysin, and chemokine (C-C motif) ligand 19 were expressed more than 30-fold with respect to nulliparous breast cells. Only three out of 20 genes [selectin P (granule membrane protein 140 kDa, antigen CD62), Fas (TNF receptor superfamily, member 6) and chemokine (C-X-C motif) ligand 11], were downregulated in parous breast with respect to nulliparous breast cells. The data lead us to conclude that an early pregnancy, by shifting the Stem cell 1 to Stem cell 2, makes the latter more easily recognized by the immune-surveillance system, which initiates the programmed cell death pathway if exposure to toxic or carcinogenic agents occurs.

Related Articles

Journal Cover

August 2007
Volume 31 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Balogh GA, Russo IH, Spittle C, Heulings R and Russo J: Immune-surveillance and programmed cell death-related genes are significantly overexpressed in the normal breast epithelium of postmenopausal parous women. Int J Oncol 31: 303-312, 2007
APA
Balogh, G.A., Russo, I.H., Spittle, C., Heulings, R., & Russo, J. (2007). Immune-surveillance and programmed cell death-related genes are significantly overexpressed in the normal breast epithelium of postmenopausal parous women. International Journal of Oncology, 31, 303-312. https://doi.org/10.3892/ijo.31.2.303
MLA
Balogh, G. A., Russo, I. H., Spittle, C., Heulings, R., Russo, J."Immune-surveillance and programmed cell death-related genes are significantly overexpressed in the normal breast epithelium of postmenopausal parous women". International Journal of Oncology 31.2 (2007): 303-312.
Chicago
Balogh, G. A., Russo, I. H., Spittle, C., Heulings, R., Russo, J."Immune-surveillance and programmed cell death-related genes are significantly overexpressed in the normal breast epithelium of postmenopausal parous women". International Journal of Oncology 31, no. 2 (2007): 303-312. https://doi.org/10.3892/ijo.31.2.303