Human chorionic gonadotropin decreases human breast cancer cell proliferation and promotes differentiation

IUBMB Life. 2014 May;66(5):352-60. doi: 10.1002/iub.1269. Epub 2014 Apr 21.

Abstract

Human chorionic gonadotropin (hCG) is a glycoprotein produced by placental trophoblasts. Previous studies indicated that hCG could be responsible for the pregnancy-induced protection against breast cancer in women. It is reported that hCG decreases proliferation and invasion of breast cancer MCF-7 cells. Our research also demonstrates that hCG can reduce the proliferation of MCF-7 cells by downregulating the expression of proliferation markers, proliferating cell nuclear antigen (PCNA), and proliferation-related Ki-67 antigen (Ki-67). Interestingly, we find here that hCG elevates the state of cellular differentiation, as characterized by the upregulation of differentiation markers, β-casein, cytokeratin-18 (CK-18), and E-cadherin. Inhibition of hCG secretion or luteinizing hormone/hCG receptors (LH/hCGRs) synthesis can weaken the effect of hCG on the induction of cell differentiation. Furthermore, hCG can suppress the expression of estrogen receptor alpha. hCG activated receptor-mediated cyclic adenosine monophosphate/protein kinase A signaling pathway. These findings indicated that a protective effect of hCG against breast cancer may be associated with its growth inhibitory and differentiation induction function in breast cancer cells.

Keywords: MCF-7 cells; breast cancer; cell differentiation; human chorionic gonadotropin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD
  • Breast Neoplasms
  • Cadherins / metabolism
  • Caseins / metabolism
  • Cell Differentiation
  • Cell Proliferation*
  • Chorionic Gonadotropin / physiology*
  • Cyclic AMP / metabolism
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism
  • Female
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Heparan Sulfate Proteoglycans / metabolism
  • Humans
  • Keratin-18 / metabolism
  • MCF-7 Cells
  • Receptors, LH / genetics
  • Receptors, LH / metabolism
  • Second Messenger Systems

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • Caseins
  • Chorionic Gonadotropin
  • ESR1 protein, human
  • Estrogen Receptor alpha
  • Heparan Sulfate Proteoglycans
  • Keratin-18
  • Receptors, LH
  • perlecan
  • Cyclic AMP