Abstract
Breast cancer outcome is highly variable. Whether inadvertent exposure to environmental xenobiotics evokes a biological response promoting cancer aggressiveness and a higher probability of tumor recurrence remains unknown. To determine specific molecular alterations which arise in high-risk breast tissue in the presence of the ubiquitous xenoestrogen, bisphenol A (BPA), we used nonmalignant random periareolar fine-needle aspirates in a novel functional assay. Early events induced by BPA in epithelial-stromal cocultures derived from the contralateral tissue of patients with breast cancer included gene expression patterns which facilitate apoptosis evasion, endurance of microenvironmental stress, and cell cycle deregulation without a detectable increase in cell numbers. This BPA response profile was significantly associated with breast tumors characterized by high histologic grade (P < 0.001) and large tumor size (P = 0.002), resulting in decreased recurrence-free patient survival (P < 0.001). Our assays show a biological "fingerprint" of probable prior exposure to endocrine-disrupting agents, and suggest a scenario in which their presence in the microenvironmental milieu of high-risk breast tissue could play a deterministic role in establishing and maintaining tumor aggressiveness and poor patient outcome.
| Original language | English |
|---|---|
| Pages (from-to) | 2076-2080 |
| Number of pages | 5 |
| Journal | Cancer Research |
| Volume | 68 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2008 Apr 1 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Bisphenol A induces a profile of tumor aggressiveness in high-risk cells from breast cancer patients. / Dairkee, Shanaz H.; Seok, Junhee; Champion, Stacey; Sayeed, Aejaz; Mindrinos, Michael; Xiao, Wenzhong; Davis, Ronald W.; Goodson, William H.
In: Cancer Research, Vol. 68, No. 7, 01.04.2008, p. 2076-2080.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Bisphenol A induces a profile of tumor aggressiveness in high-risk cells from breast cancer patients
AU - Dairkee, Shanaz H.
AU - Seok, Junhee
AU - Champion, Stacey
AU - Sayeed, Aejaz
AU - Mindrinos, Michael
AU - Xiao, Wenzhong
AU - Davis, Ronald W.
AU - Goodson, William H.
PY - 2008/4/1
Y1 - 2008/4/1
N2 - Breast cancer outcome is highly variable. Whether inadvertent exposure to environmental xenobiotics evokes a biological response promoting cancer aggressiveness and a higher probability of tumor recurrence remains unknown. To determine specific molecular alterations which arise in high-risk breast tissue in the presence of the ubiquitous xenoestrogen, bisphenol A (BPA), we used nonmalignant random periareolar fine-needle aspirates in a novel functional assay. Early events induced by BPA in epithelial-stromal cocultures derived from the contralateral tissue of patients with breast cancer included gene expression patterns which facilitate apoptosis evasion, endurance of microenvironmental stress, and cell cycle deregulation without a detectable increase in cell numbers. This BPA response profile was significantly associated with breast tumors characterized by high histologic grade (P < 0.001) and large tumor size (P = 0.002), resulting in decreased recurrence-free patient survival (P < 0.001). Our assays show a biological "fingerprint" of probable prior exposure to endocrine-disrupting agents, and suggest a scenario in which their presence in the microenvironmental milieu of high-risk breast tissue could play a deterministic role in establishing and maintaining tumor aggressiveness and poor patient outcome.
AB - Breast cancer outcome is highly variable. Whether inadvertent exposure to environmental xenobiotics evokes a biological response promoting cancer aggressiveness and a higher probability of tumor recurrence remains unknown. To determine specific molecular alterations which arise in high-risk breast tissue in the presence of the ubiquitous xenoestrogen, bisphenol A (BPA), we used nonmalignant random periareolar fine-needle aspirates in a novel functional assay. Early events induced by BPA in epithelial-stromal cocultures derived from the contralateral tissue of patients with breast cancer included gene expression patterns which facilitate apoptosis evasion, endurance of microenvironmental stress, and cell cycle deregulation without a detectable increase in cell numbers. This BPA response profile was significantly associated with breast tumors characterized by high histologic grade (P < 0.001) and large tumor size (P = 0.002), resulting in decreased recurrence-free patient survival (P < 0.001). Our assays show a biological "fingerprint" of probable prior exposure to endocrine-disrupting agents, and suggest a scenario in which their presence in the microenvironmental milieu of high-risk breast tissue could play a deterministic role in establishing and maintaining tumor aggressiveness and poor patient outcome.
UR - http://www.scopus.com/inward/record.url?scp=42049098601&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=42049098601&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-07-6526
DO - 10.1158/0008-5472.CAN-07-6526
M3 - Article
C2 - 18381411
AN - SCOPUS:42049098601
VL - 68
SP - 2076
EP - 2080
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 7
ER -