Homeobox A7 increases cell proliferation by up-regulation of epidermal growth factor receptor expression in human granulosa cells.
BACKGROUND
Homeobox (HOX) genes encode transcription factors, which regulate cell proliferation, differentiation, adhesion, and migration. The deregulation of HOX genes is frequently associated with human reproductive system disorders. However, knowledge regarding the role of HOX genes in human granulosa cells is limited.


METHODS
To determine the role of HOXA7 in the regulation and associated mechanisms of cell proliferation in human granulosa cells, HOXA7 and epidermal growth factor receptor (EGFR) expressions were examined in primary granulosa cells (hGCs), an immortalized human granulosa cell line, SVOG, and a granulosa tumor cell line, KGN, by real-time PCR and Western blotting. To manipulate the expression of HOXA7, the HOXA7 specific siRNA was used to knockdown HOXA7 in KGN. Conversely, HOXA7 was overexpressed in SVOG by transfection with the pcDNA3.1-HOAX7 vector. Cell proliferation was measured by the MTT assay.


RESULTS
Our results show that HOXA7 and EGFR were overexpressed in KGN cells compared to hGCs and SVOG cells. Knockdown of HOXA7 in KGN cells significantly decreased cell proliferation and EGFR expression. Overexpression of HOXA7 in SVOG cells significantly promoted cell growth and EGFR expression. Moreover, the EGF-induced KGN proliferation was abrogated, and the activation of downstream signaling was diminished when HOXA7 was knocked down. Overexpression of HOXA7 in SVOG cells had an opposite effect.


CONCLUSIONS
Our present study reveals a novel mechanistic role for HOXA7 in modulating granulosa cell proliferation via the regulation of EGFR. This finding contributes to the knowledge of the pro-proliferation effect of HOXA7 in granulosa cell growth and differentiation.
Zhang
Yu
Y
Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, China.
Huang
Qing
Q
Cheng
Jung-Chien
JC
Nishi
Yoshihiro
Y
Yanase
Toshihiko
T
Huang
He-Feng
HF
Leung
Peter C K
PC
D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics / Q000502:physiology
C115962:HOXA7 protein, human; D018398:Homeodomain Proteins; D034741:RNA, Small Interfering; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D051058:Oncogene Protein v-akt