Significance of PELP1 in ER-negative breast cancer metastasis

Sudipa Roy, Dimple Chakravarty, Valerie Cortez, Keya De Mukhopadhyay, Abhik Bandyopadhyay, Jung Mo Ahn, Ganesh V. Raj, Rajeshwar R. Tekmal, LuZhe Sun, Ratna K. Vadlamudi

Research output: Contribution to journalArticle

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Abstract

Breast cancer metastasis is a major clinical problem. The molecular basis of breast cancer progression to metastasis remains poorly understood. PELP1 is an estrogen receptor (ER) coregulator that has been implicated as a proto-oncogene whose expression is deregulated in metastatic breast tumors and whose expression is retained in ERnegative tumors.Weexamined the mechanism and significance of PELP1-mediated signaling in ER-negative breast cancer progression using two ER-negative model cells (MDA-MB-231 and 4T1 cells) that stably express PELP1- shRNA. These model cells had reduced PELP1 expression (75% of endogenous levels) and exhibited less propensity to proliferate in growth assays in vitro. PELP1 downregulation substantially affected migration of ER-negative cells in Boyden chamber and invasion assays. Using mechanistic studies, we found that PELP1 modulated expression of several genes involved in the epithelial mesenchymal transition (EMT), including MMPs, SNAIL, TWIST, and ZEB. In addition, PELP1 knockdown reduced the in vivo metastatic potential of ER-negative breast cancer cells and significantly reduced lung metastatic nodules in a xenograft assay. These results implicate PELP1 as having a role in ER-negative breast cancer metastasis, reveal novel mechanism of coregulator regulation of metastasis via promoting cell motility/EMT by modulating expression of genes, and suggest PELP1 may be a potential therapeutic target for metastatic ER-negative breast cancer.

Original languageEnglish (US)
Pages (from-to)25-33
Number of pages9
JournalMolecular Cancer Research
Volume10
Issue number1
DOIs
StatePublished - Jan 2012

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Estrogen Receptors
Breast Neoplasms
Neoplasm Metastasis
Epithelial-Mesenchymal Transition
Gene Expression
Proto-Oncogenes
Matrix Metalloproteinases
Heterografts
Small Interfering RNA
Cell Movement
Down-Regulation
Lung
Growth
Neoplasms

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Oncology

Cite this

Roy, S., Chakravarty, D., Cortez, V., De Mukhopadhyay, K., Bandyopadhyay, A., Ahn, J. M., ... Vadlamudi, R. K. (2012). Significance of PELP1 in ER-negative breast cancer metastasis. Molecular Cancer Research, 10(1), 25-33. https://doi.org/10.1158/1541-7786.MCR-11-0456

Significance of PELP1 in ER-negative breast cancer metastasis. / Roy, Sudipa; Chakravarty, Dimple; Cortez, Valerie; De Mukhopadhyay, Keya; Bandyopadhyay, Abhik; Ahn, Jung Mo; Raj, Ganesh V.; Tekmal, Rajeshwar R.; Sun, LuZhe; Vadlamudi, Ratna K.

In: Molecular Cancer Research, Vol. 10, No. 1, 01.2012, p. 25-33.

Research output: Contribution to journalArticle

Roy, S, Chakravarty, D, Cortez, V, De Mukhopadhyay, K, Bandyopadhyay, A, Ahn, JM, Raj, GV, Tekmal, RR, Sun, L & Vadlamudi, RK 2012, 'Significance of PELP1 in ER-negative breast cancer metastasis', Molecular Cancer Research, vol. 10, no. 1, pp. 25-33. https://doi.org/10.1158/1541-7786.MCR-11-0456
Roy S, Chakravarty D, Cortez V, De Mukhopadhyay K, Bandyopadhyay A, Ahn JM et al. Significance of PELP1 in ER-negative breast cancer metastasis. Molecular Cancer Research. 2012 Jan;10(1):25-33. https://doi.org/10.1158/1541-7786.MCR-11-0456
Roy, Sudipa ; Chakravarty, Dimple ; Cortez, Valerie ; De Mukhopadhyay, Keya ; Bandyopadhyay, Abhik ; Ahn, Jung Mo ; Raj, Ganesh V. ; Tekmal, Rajeshwar R. ; Sun, LuZhe ; Vadlamudi, Ratna K. / Significance of PELP1 in ER-negative breast cancer metastasis. In: Molecular Cancer Research. 2012 ; Vol. 10, No. 1. pp. 25-33.
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